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Pharmaceutical significance of Schiff bases: an overview


Schiff bases are a diverse group of organic compounds with great pharmaceutical importance due to the presence of carbon–nitrogen double bonds (–C=N–). These compounds are synthesized by the condensation reaction between a primary amine and an aldehyde or ketone in a suitable solvent such as methanol. These compounds have shown antibacterial, antifungal, antiviral, anti-inflammatory, and antioxidant activities, which have garnered the attention of organic chemists in synthesizing these compounds. Recent advances have been summarized in this review paper mainly including compounds with potential antibacterial, antifungal, and antiviral activities. Synthetic schemes are included to provide a better understanding of the Schiff base synthesis mechanism. This review paper will provide a way forward for the pharmaceutical chemist to synthesize new compounds with potential biological activities.

Graphical abstract


Hugo Schiff initially described in 1864, the synthesis of Schiff bases by a condensation reaction between a primary amine and multiple carbonyl compounds [1,2,3,4,5,6]. These Schiff bases are mostly referred to as the azomethine group represented in organic chemistry as RHC=N–R1 [7, 8]. The corresponding alkyl, aryl, or heterocyclic groups can be the R or R1 in Schiff bases. The Schiff bases are mostly referred to as the imines or the azomethine groups in synthetic chemistry [9, 10]. The presence of lone pairs is attributed to its sp2 hybridization as the compound is highly reactive due to carbon and nitrogen atoms. Due to the presence of strong properties like adaptability, simplicity, and functionality, these compounds are of high importance [11, 12]. The significance is of high importance in biological assays that the Schiff bases can form diverse functional groups. An advanced approach to the existing nature of Schiff bases can be helpful nature to tackling the biological gaps and increasing the efficacy of Schiff base drugs [13,14,15,16,17] (Fig. 1).

Fig. 1
figure 1

General structure of Schiff bases

The discovery of Schiff bases dates back to the nineteenth century during which a chemist named “Hugo Schiff” first documented a reaction showing condensation between amines and carbonyl functional groups [13, 18,19,20,21]. In contemporary times, this domain of scientific inquiry about Schiff base coordination chemistry has seen significant growth and expansion [22, 23]. The significance of Schiff base complexes in the fields of material science, biomedical applications, bioinorganic chemistry, encapsulation processes, supramolecular chemistry, catalysis, and separation, and the generation of molecules with exceptional characteristics and structures has been widely acknowledged and extensively examined in the existing literature [24,25,26,27]. The literature has documented the use of Schiff bases derived from salicylaldehydes as agents for regulating plant development, as well as exhibiting antibacterial or antimycotic properties [28,29,30]. Schiff bases have been shown to possess analytical uses as well. The significance of these bases helps explain the difficult mechanisms inside biological systems and gives proper meaning to the imine group activity. These also provide broad-spectrum activity against several species, including Candida, Plasmopora viticola, Trichophyton gypsum, Staphylococcus aureus, Erysiphe graminis, Mycobacterium, Albicans, Bacillus polymyxa, and Escherichia coli [31,32,33,34].

Furthermore, the Schiff bases are significant in metal complexes due to their unique ability to form a structure holding transition central metals with the reactants of the condensation reaction as illustrated in the literature for metals like Hg(II), Gd(III), Cu(II), Co(II), Ni(II), Zn(II), Y(III), Al(III), Pb(II), and Ag(II) [35,36,37,38,39,40,41,42,43,44]. Extensive research has been conducted on Schiff bases due to their significant catalytic characteristics. These compounds exhibit catalytic properties when used in the process of hydrogenating olefins. Biomimetic catalytic processes are applicable in several contexts. One intriguing use of Schiff bases is in their utilization as a very efficient corrosion inhibitor, owing to their inherent capability to autonomously generate a monolayer on the targeted surface for protection. Numerous commercial inhibitors often include aldehydes or amines; nevertheless, it is hypothesized that the enhanced efficacy seen in some instances is attributed to the presence of Schiff bases, likely owing to the presence of the C=N link [45,46,47,48]. Chemisorption is the primary mode of combination and the combinatorial mechanism of metals with inhibitors. The inhibitor molecule needs to possess active sites that are capable of establishing chemical connections with the metal surface via the process of electron transfer. In instances of this kind, the metal functions as an electrophile, while the inhibitor assumes the role of a Lewis base. The protective chemical has nucleophilic centers, namely oxygen and nitrogen atoms, that possess unshared electron pairs that are easily accessible for electron sharing. In conjunction with the atoms of the benzene rings, these entities provide several absorption sites for the inhibitor, facilitating the establishment of a stable monolayer [49,50,51]. The biological features of Schiff bases, including their antibacterial and antifungal activity, have been documented in the literature. Metal complexes have garnered significant attention in the scientific community due to their extensive investigation and exploration, primarily owing to their potential use in anticancer and herbicidal contexts. These organisms function as exemplars for species that have significant biological importance [52,53,54,55,56,57,58].

Main text

Pharmaceutical significance of Schiff bases


Antimicrobials are well recognized as a very effective therapeutic approach in the field of medicine [59]. However, the efficacy of antimicrobials is significantly hindered by the emergence of antibiotic-resistant bacteria. The formation of Schiff bases of amino acids was achieved by the condensation reaction between isatin and several amino acids, including phenylalanine, leucine, cysteine, alanine, valine, and glycine. These amino acids exhibited notable antibacterial efficacy [60, 61]. Schiff bases derived from cellulose are produced by the condensation reaction between p-aminophenol and aldehyde moieties and have shown antibacterial efficacy against, Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis [62].

A new collection of aromatic Schiff bases was prepared using a reflux (condensation) reaction between 5-aminopyrazoles and aromatic aldehydes [63]. The synthesis process yielded large quantities of the desired compounds. These Schiff bases were then assessed for their antibacterial efficacy through in vitro experiments against “multi-drug resistant bacteria (MDRB).” In normal circumstances, the majority of the compounds of Schiff bases exhibited superior biological efficacy. Furthermore, the molecular docking investigation revealed that kinase inhibition had a beneficial impact on the activity of dihydrofolate reductase enzymes and Staphylococcus aureus DNA gyrase. In addition, the data for drug-likeness indicated that these compounds under investigation satisfy the criteria outlined by Lipinski's rule and exhibit favorable biological drug scores for various activities [64]. The first findings about the Schiff base's effectiveness in combating MDRB have significant potential as a framework for the identification of novel medicines by derivatization or modification (Scheme 1).

Scheme 1
scheme 1

Synthesis of Schiff Bases 7–18 [63]

The reaction included the utilization of heteroaromatic aldehydes, which were separately reacted with aminoanthracene and aminopyrene. As a result, new Schiff base derivatives 19a–19f and 20a–20f were produced with high yields [65]. The novel synthesized compounds were subjected to several tests to evaluate their reducing power, metal chelating, DNA binding abilities, antibacterial, and free radical scavenging [66]. The radical scavenging activity of the series of compounds was much superior to that of the 19 series compounds. The compound 19c exhibited the greatest metal chelating activity. In three antioxidant test methods, the standards demonstrated greater antioxidant activity compared to the DMSO solution of chemicals. Furthermore, it was shown that both compounds exhibited potential bacterial resistance activity against the employed microorganisms. Additionally, both compounds had a strong affinity for binding to CT-DNA. The findings of this research suggest that the recently examined compounds possess the ability to attach to DNA, making them promising candidates for cancer therapy. However, it is recommended that their structural composition be further modified in further investigations [67, 68] (Scheme 2).

Scheme 2
scheme 2

Synthesis of anthracene- and pyrene-based Schiff base derivatives [65]

A total of twelve Schiff bases (21a–27a, 21b–25b) were synthesized by the reaction of isatin and 5-bromoisatin with various anilines as shown in Scheme 3. The synthesis process used green chemistry principles, specifically using microwave (MW) and ultrasonic (US) assistance. The antimicrobial efficacy of each chemical was assessed against a total of nine bacterial strains, including both standard and clinical isolates, using the Agar-well diffusion technique. The minimum inhibitory concentration against Pseudomonas aeruginosa for 21a and 21b was found to be 78 µg/mL, which is the lowest value obtained. The identification of all synthesized substances was accomplished by the use of multiple characterization techniques including ultra-violet spectroscopy, proton nuclear magnetic resonance, infrared spectroscopy, caron-13 nuclear magnetic resonance, and microanalysis. The antibacterial activity for newly synthesized Schiff bases was rationalized by using the “Molecular Electrostatic Potential Surface (MEPS) analysis” and “Quantitative Structure–Activity Relationship (QSAR).” The findings of the QSAR analysis, which included density functional theory (DFT)-based, steric, and hydrophobic descriptors, indicate that compounds exhibiting higher hydrophobicity and lower dipole moment have antibacterial properties against “Klebsiella pneumoniae ATCC700603” [69].

Scheme 3
scheme 3

Synthetic route of Schiff bases of isatin [69]

According to the processes shown in Scheme 4, chlorobenzene aldehydes were reacted with amino derivatives like L-cysteine by condensing the reactants in a solvent methanol to produce Schiff base 28, and methoxybenzene aldehydes were reacted with the amino mercapto acids by condensing in a solvent methanol to produce Schiff base 29. The yields for compounds 1 and 2 were outstanding (77% and 85%, respectively) [70]. TLC was used to evaluate the reaction's progression and the purity of the synthesized compounds. The stationary phase used was of silica gel and the mobile phase was of methanol which ascended higher in the chromatogram. FT-IR, 13C, and 1H, NMR spectroscopy were used to characterize the synthesized compounds 28 and 29. With compound 28 having more antibacterial activity than compound 29, the newly synthesized Schiff bases demonstrated action against the aforementioned microbes. The Schiff base 1 is a little reactive and more stable in a biological environment according to the estimated global chemical reactivity indices. However, further research will be needed in the future to fully understand the mechanism of these chemicals' antibacterial effects [71].

Scheme 4
scheme 4

Synthesis of Schiff compounds [70]

Schiff base compounds have broad use across several domains, including organic, inorganic, analytical, and biological disciplines. In the contemporary period, pharmacology applications have exceptional potential and are extensively used within the pharmaceutical sector. A recent study based on the antibacterial activity of Schiff bases was carried out by reacting the compounds in a way to produce two main compounds named DmChDp (2,2′-(5,5-dimethylcyclohexane-1,3-diylidene)bis(azan-1-yl-1-ylidene)diphenol) and the DmChDa (N,N′-(5,5-dimethylcyclohexane-1,3-diylidene)dianiline). These newly synthesized Schiff bases have gained a lot of attention due to their diverse and significant antibiological activities against the strains of Staphylococcus aureus. The ligand interactions were also studied to understand the pro-drug-like features that aided in the efficacy of the final products. The characterization techniques included the docking process and the analysis using traditional spectroscopic techniques. The biological activities were evaluated against the six given proteins derived from S. aureus. The newly formed Schiff bases showed a great inhibitory effect for bacteria and helped in increasing the efficiency of drugs [17] (Scheme 5).

Scheme 5
scheme 5

Structure of 30) DmChDp 31) DmChDa Schiff bases [17]

In brief, a series of new lanthanide complexes were synthesized by the use of Schiff base ligands, together with a “benzimidazole moiety.” These complexes were thoroughly characterized by utilizing several analytical methodologies, ensuring their unambiguous identification and understanding. Initial experiments for the compounds were performed to assess various pharmacological uses of the substances under investigation. These assessments were undertaken using a range of bioassays, including tests for antiproliferative activity, antiparasitic activity, and antibacterial activity. The findings indicate that the biological activities of the compounds are influenced by structural modifications. Specifically, ligands L1 and L2, along with their metal complexes, demonstrated minimum inhibitory concentration (MIC) values in comparison with ligands L3 and L4 and their respective complexes. This disparity in MIC values may be attributed to substitutions on the “aminophenol ring.” In a similar vein, it was shown that the compounds had an impact on the fluidity of the cell membrane by modifying the hydrophobic region inside the lipid bilayer. This observation suggests a possible correlation between such alterations and the potential therapeutic uses of these compounds. The aforementioned result has the potential to serve as a valuable point of reference in future endeavors aimed at the advancement of novel pharmacological medicines. Ongoing investigations in the laboratory are now exploring the impact of the alterations on the molecular architecture. This research aimed to provide deeper insights into the mechanism of action associated with these particular molecules [72] (Scheme 6).

Scheme 6
scheme 6

Synthesis of Lanthanide complex Schiff bases [72]


The recent work included the chemical modification using diabetic insulin structure by the Schiff bases introduction onto the main chain of the reactant. Approximately six different derivatives of the insulin were produced by a simple method, and structures were characterized using FT-IR, proton NMR, and carbon-13 NMR spectroscopic techniques [73]. The structures exhibited variations in the quantity and positional substitution benzene ring using the phenoxide ions or phenolic groups. Following this, further research was conducted to investigate their biological properties, specifically focusing on their antioxidant and antifungal actions. The assessment of antioxidant activity included the determination of scavenging capacities toward superoxide radicals, hydroxyl radicals, and DPPH radicals in addition to antioxidant activities. These activities were of inulin which has shown a considerable enhancement in comparison with that of inulin. In addition, the in vitro evaluation of antifungal activity against three types of plant pathogenic fungus was conducted using the mycelium growth rate technique [15, 74]. The antifungal activity of the inulin derivatives was found to be much higher when compared to that of pure inulin. The biological activity of the inulin derivatives was influenced by many parameters, such as the degree of substitution (DS), as well as the quantity and location of phenolic hydroxyl groups. The products elucidated in this manuscript show significant promise as biomaterials characterized by favorable bioactivity and biocompatibility. Further investigation of the structure–activity link is warranted in future research endeavors [75, 76] (Scheme 7).

Scheme 7
scheme 7

Synthesis of Schiff bases [73]

The synthesis of Schiff base derivatives of sulfa drugs involved the condensation of commercially available sulfa drugs, namely sulfamethoxazole, sulfamethazine, and Sulfamethoxypyridazine, with suitable “substituted aromatic aldehydes.” A variety of solvents with different levels of polarity were used to optimize the reaction conditions. Ultimately, a solvent combination consisting of ethanol and a small amount of acetic acid was determined to be the most suitable for the condensation processes, as shown in Scheme 8. In all instances, a stoichiometric amount of “sulfonamides and substituted aromatic aldehydes” was used, resulting in reaction yields ranging from 35 to 92%. The purification of the compounds was conducted using either recrystallization or liquid column chromatography before their characterization. It was ensured that all compounds had a minimum purity of 95% before they were deemed suitable for microbiological examination [77].

Scheme 8
scheme 8

Reaction condition for the synthesis of Schiff base derivatives (32a-32h) of aminobenzenesulfonamied [77]

The present work effectively synthesized a range of chitosan derivatives containing active halogenated aromatic imines by the formation of Schiff bases, resulting in high degrees of substitution. The structural characterization of the sample was conducted via the use of elemental analysis, solid-state 13C nuclear magnetic resonance (NMR) spectroscopy, and Fourier transforms infrared (FT-IR) spectroscopy. Additionally, an examination was conducted to assess the antifungal efficacy against three prevalent plant pathogenic fungi, namely Botrytis cinerea, Fusarium oxysporum f. sp. cucumerinum, and Fusarium oxysporum f. sp. niveum, by in vitro hyphal measurements. The findings of the study indicate that the antifungal activity of double Schiff bases of chitosan derivatives was much higher than that of chitosan, particularly at a concentration of 1.0 mg/mL. The chitosan derivatives with dual Schiff bases, including halogenated benzene moieties, exhibited inhibitory indices of 95% at a concentration of 1.0 mg/mL against Botrytis cinerea. This high inhibitory activity may be attributed to the higher electron-withdrawing nature of the halogen substituents. The increased degree of substitution was shown to have a good impact on enhancing the antifungal activity. This work presents a pragmatic approach for the synthesis of novel double Schiff bases of chitosan derivatives including halogeno-benzenes, with the potential for further development as potent antifungal drugs [78] (Scheme 9).

Scheme 9
scheme 9

Synthesis pathway for double Schiff bases of Chitosan [78]


In this study, a series of novel Schiff base ligands were synthesized by reacting 5-amino-4-phenyl-4H-1,2,4-triazole-3-thiol 33 with various substituted benzaldehydes (34a-34d). Additionally, metal complexes of these ligands with Cu(II), Fe(II), Au(III), and Mn(II) were also prepared. The synthesis of a novel benzothiazole derivative (37) was achieved by the reaction between the reactant compound and N-(benzothiazol-2-yl)-2-chloroacetamide through coupling. The spectral qualities of the subject were examined. The anti-HIV-1 and HIV-2 activity of the recently developed and synthesized Schiff base ligands and their corresponding metal complexes were evaluated by the analysis of their ability to suppress “HIV-induced cytopathogenicity in MT-4 cells.” Compounds 37 exhibited significant inhibitory activity in cell culture against HIV1, with EC50 values of 12.2 μg/mL (selectivity index (SI) = 4) and > 2.11 μg/mL (SI =  > 1), respectively. Compound 11 also demonstrated inhibition against HIV-2, with an EC50 value above 10.2 μg/mL and a selectivity index of 9. This finding suggests that compound 37 has promise as a potential candidate for further refinement and enhancement [79] (Scheme 10).

Scheme 10
scheme 10

Reagents and conditions i) EtOH, reflux, 2h; ii) 36, K2CO3, acetone, 20 °C, then flux [79]

A novel series comprising 3-(benzylideneamino) compounds has been developed. The synthesis of 2-phenylquinazoline-4(3H)-ones included the production of Schiff bases from 3-amino compounds. The reaction of -2-phenyl quinazoline-4(3)H-one with several carbonyl compounds that have been replaced. The chemical structures of the compounds were determined by the use of spectrum analysis. The cytotoxicity and antiviral activity of the tested compounds were assessed against a range of viruses, including influenza B virus, influenza A H3N2 subtype, influenza A H1N1 subtype, vaccinia virus, feline herpes virus, herpes simplex virus-1 TK-KOS ACVr, Punta Toro virus, herpes simplex virus-2 (G), para influenza-3 virus, reovirus-1, Sindbis virus, Coxsackie virus B4, vesicular stomatitis virus, respiratory syncytial virus herpes simplex virus-1 (KOS), and feline coronavirus (FIPV). A compound formed exhibited superior antiviral efficacy against all evaluated viral strains [80] (Scheme 11).

Scheme 11
scheme 11

Synthetic route for the title compounds [80]

This study presents a unique way to synthesize novel pro-drugs such as abacavir using nitrogen substitution using different ketone and substituted benzaldehyde derivatives. The results of the in vitro experiments demonstrated that compound (3-(2-(4-methylaminobenzylideneamino)-6-(cyclopropylamino)-9H-purin-9-yl)cyclopentyl)methanol (38c) exhibited the highest level of effectiveness against HIV, as shown by its EC50 value of 0.05 lM. Furthermore, the compound had an EC50 value above 100 lM, resulting in a selectivity index greater than 2000. Compound 38c exhibited a much higher potency compared to the original medication, with a 32-fold increase in activity as shown by its EC50 value of 1.6 lM. At a pH of 7.4 and a temperature of 37 °C, the hydrolytic half-life (t1/2) exhibited a range of 120 to 240 min [81] (Scheme 12).

Scheme 12
scheme 12

Synthesis of Schiff bases derivatives of Abacavir [81]


The pharmaceutical significance of Schiff bases has gained a lot of attention and this review focuses on giving an insight into the antibacterial, antifungal, and antiviral activities. The Schiff base-derived antibacterial drugs showed significant activities against bacteria by structural modifications while antifungal drugs proved to treat skin diseases mainly. The antiviral Schiff base drugs are currently being used against viral diseases such as influenza, herpes simplex, and HIV. The given literature also explains the mechanism by which the different products are synthesized and their potential activating groups. Furthermore, activities detail for various microorganisms is given which will help chemists to evaluate further compounds. The inhibitory effects of given compounds are also discussed. Overall, this review is a thoughtful and promising contribution to the field of Schiff bases that will bring positive outcomes in the future.

Availability of data and materials

The data that support the findings of this study are available from the corresponding author, upon reasonable request.



Multi-drug resistant bacteria


Dimethyl sulfoxide






Nuclear magnetic resonance


Molecular electrostatic potential surface


Quantitative structure–activity relationship






Half maximal effective concentration


Circulating tumor DNA


  1. Berhanu AL, Mohiuddin I, Malik AK, Aulakh JS, Kumar V, Kim KH (2019) A review of the applications of Schiff bases as optical chemical sensors. TrAC Trends Anal Chem 116:74–91

    Article  CAS  Google Scholar 

  2. Abu-Dief AM, Mohamed IM (2015) A review of versatile applications of transition metal complexes incorporating Schiff bases. Beni-suef Univ J Basic Appl Sci 4(2):119–133

    PubMed  PubMed Central  Google Scholar 

  3. Juyal VK, Pathak A, Panwar M, Thakuri SC, Prakash O, Agrwal A, Nand V (2023) Schiff base metal complexes as a versatile catalyst: a review. J Organomet Chem 2023:122825

    Article  Google Scholar 

  4. Boulechfar C, Ferkous H, Delimi A, Djedouani A, Kahlouche A, Boublia A, Benguerba Y (2023) Schiff bases and their metal complexes: a review on the history, synthesis, and applications. Inorg Chem Commun 150:110451

    Article  CAS  Google Scholar 

  5. Ashraf T, Ali B, Qayyum H, Haroone MS, Shabbir G (2023) Pharmacological aspects of Schiff base metal complexes: a critical review. Inorg Chem Commun 150:110449

    Article  CAS  Google Scholar 

  6. Alam MZ, Alimuddin, Khan SA (2023) A review on Schiff base as a versatile fluorescent chemo-sensors tool for detection of Cu2+ and Fe3+ metal ion. J Fluoresc 33:1–32

    Article  Google Scholar 

  7. Hameed A, Al-Rashida M, Uroos M, Abid Ali S, Khan KM (2017) Schiff bases in medicinal chemistry: a patent review (2010–2015). Expert Opin Ther Pat 27(1):63–79

    Article  CAS  PubMed  Google Scholar 

  8. Manvatkar VD, Patle RY, Meshram PH, Dongre RS (2023) Azomethine-functionalized organic–inorganic framework: an overview. Chem Pap 77:1–22

    Article  Google Scholar 

  9. Uddin MN, Ahmed SS, Alam SR (2020) Biomedical applications of Schiff base metal complexes. J Coord Chem 73(23):3109–3149

    Article  CAS  Google Scholar 

  10. Li M, Cheng Z, Sun J, Tian Y, He J, Chen Y, Liu Z (2023) Nitrogen-doped porous carbon nanosheets based on a Schiff base reaction for high-performance lithium-ion batteries anode. Energies 16(4):1733

    Article  Google Scholar 

  11. Antony R, Arun T, Manickam STD (2019) A review on applications of chitosan-based Schiff bases. Int J Biol Macromol 129:615–633

    Article  CAS  PubMed  Google Scholar 

  12. Yadav M, Yadav D, Singh DP, Kapoor JK (2023) Pharmaceutical properties of macrocyclic Schiff base transition metal complexes: urgent need in today’s world. Inorg Chim Acta 546:121300

    Article  CAS  Google Scholar 

  13. Zhang J, Xu L, Wong WY (2018) Energy materials based on metal Schiff base complexes. Coord Chem Rev 355:180–198

    Article  CAS  Google Scholar 

  14. Jia Y, Li J (2015) Molecular assembly of Schiff base interactions: construction and application. Chem Rev 115(3):1597–1621

    Article  CAS  PubMed  Google Scholar 

  15. Al Zoubi W, Al-Hamdani AAS, Kaseem M (2016) Synthesis and antioxidant activities of Schiff bases and their complexes: a review. Appl Organomet Chem 30(10):810–817

    Article  CAS  Google Scholar 

  16. El-Sonbati AZ, Mahmoud WH, Mohamed GG, Diab MA, Morgan SM, Abbas SY (2019) Synthesis, characterization of Schiff base metal complexes and their biological investigation. Appl Organomet Chem 33(9):e5048

    Article  Google Scholar 

  17. Kakkassery JT, Raphael VP, Johnson R (2021) In vitro antibacterial and in silico docking studies of two Schiff bases on Staphylococcus aureus and its target proteins. Future J Pharm Sci 7(1):1–9

    Google Scholar 

  18. Iacopetta D, Ceramella J, Catalano A, Saturnino C, Bonomo MG, Franchini C, Sinicropi MS (2021) Schiff bases: interesting scaffolds with promising antitumoral properties. Appl Sci 11(4):1877

    Article  CAS  Google Scholar 

  19. Qin W, Long S, Panunzio M, Biondi S (2013) Schiff bases: a short survey on an evergreen chemistry tool. Molecules 18(10):12264–12289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chaturvedi D, Kamboj M (2016) Role of Schiff base in drug discovery research. Chem Sci J 7(2):7–8

    Article  Google Scholar 

  21. Parveen S (2020) Recent advances in anticancer ruthenium Schiff base complexes. Appl Organomet Chem 34(8):e5687

    Article  CAS  Google Scholar 

  22. Udhayakumari D, Inbaraj V (2020) A review on Schiff base fluorescent chemosensors for cell imaging applications. J Fluoresc 30:1203–1223

    Article  CAS  PubMed  Google Scholar 

  23. Collinson SR, Fenton DE (1996) Metal complexes of bibracchial Schiff base macrocycles. Coord Chem Rev 148:19–40

    Article  CAS  Google Scholar 

  24. Xu J, Liu Y, Hsu SH (2019) Hydrogels based on Schiff base linkages for biomedical applications. Molecules 24(16):3005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ghanghas P, Choudhary A, Kumar D, Poonia K (2021) Coordination metal complexes with Schiff bases: useful pharmacophores with comprehensive biological applications. Inorg Chem Commun 130:108710

    Article  CAS  Google Scholar 

  26. Verma C, Quraishi MA (2021) Recent progresses in Schiff bases as aqueous phase corrosion inhibitors: design and applications. Coord Chem Rev 446:214105

    Article  CAS  Google Scholar 

  27. Matar SA, Talib WH, Mustafa MS, Mubarak MS, AlDamen MA (2015) Synthesis, characterization, and antimicrobial activity of Schiff bases derived from benzaldehydes and 3,3′-diaminodipropylamine. Arab J Chem 8(6):850–857

    Article  CAS  Google Scholar 

  28. Liu X, Manzur C, Novoa N, Celedón S, Carrillo D, Hamon JR (2018) Multidentate unsymmetrically-substituted Schiff bases and their metal complexes: synthesis, functional materials properties, and applications to catalysis. Coord Chem Rev 357:144–172

    Article  CAS  Google Scholar 

  29. Shakir M, Hanif S, Sherwani MA, Mohammad O, Al-Resayes SI (2015) Pharmacologically significant complexes of Mn (II), Co (II), Ni (II), Cu (II) and Zn (II) of novel Schiff base ligand,(E)-N-(furan-2-yl methylene) quinolin-8-amine: Synthesis, spectral, XRD, SEM, antimicrobial, antioxidant and in vitro cytotoxic studies. J Mol Struct 1092:143–159

    Article  ADS  CAS  Google Scholar 

  30. Balakrishnan B, Joshi N, Banerjee R (2013) Borate aided Schiff’s base formation yields in situ gelling hydrogels for cartilage regeneration. J Mater Chem B 1(41):5564–5577

    Article  CAS  PubMed  Google Scholar 

  31. Yousif E, Majeed A, Al-Sammarrae K, Salih N, Salimon J, Abdullah B (2017) Metal complexes of Schiff base: preparation, characterization and antibacterial activity. Arab J Chem 10:S1639–S1644

    Article  CAS  Google Scholar 

  32. Liu X, Hamon JR (2019) Recent developments in penta-, hexa-and heptadentate Schiff base ligands and their metal complexes. Coord Chem Rev 389:94–118

    Article  CAS  Google Scholar 

  33. More MS, Joshi PG, Mishra YK, Khanna PK (2019) Metal complexes driven from Schiff bases and semicarbazones for biomedical and allied applications: a review. Mater Today Chem 14:100195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. El-Gammal OA, Mohamed FS, Rezk GN, El-Bindary AA (2021) Structural characterization and biological activity of a new metal complexes based of Schiff base. J Mol Liq 330:115522

    Article  CAS  Google Scholar 

  35. Shellaiah M, Rajan YC, Balu P, Murugan A (2015) A pyrene based Schiff base probe for selective fluorescence turn-on detection of Hg2+ ions with live cell application. New J Chem 39(4):2523–2531

    Article  CAS  Google Scholar 

  36. Keshavarzian E, Asadi Z, Poupon M, Dusek M, Rastegari B (2022) Heterodinuclear Cu–Gd (3d–4f) complex with di-compartmental Schiff base ligand in biological activity: synthesis, crystal structure, catecholase activity and DNA & BSA-binding studies. J Mol Liq 345:117785

    Article  CAS  Google Scholar 

  37. Bitu MNA, Hossain MS, Zahid AASM, Zakaria CM, Kudrat-E-Zahan M (2019) Anti-pathogenic activity of cu (II) complexes incorporating Schiff bases: a short review. Am J Heterocyclic Chem 5(1):11–23

    Article  Google Scholar 

  38. Spinu C, Kriza A (2000) Co (II), Ni (II) and Cu (II) complexes of bidentate Schiff bases. Acta Chim Slov 47(2):179–186

    CAS  Google Scholar 

  39. Sorochinsky AE, Aceña JL, Moriwaki H, Sato T, Soloshonok VA (2013) Asymmetric synthesis of α-amino acids via homologation of Ni (II) complexes of glycine Schiff bases; Part 1: alkyl halide alkylations. Amino Acids 45:691–718

    Article  CAS  PubMed  Google Scholar 

  40. Liu J, Wu BW, Zhang B, Liu Y (2006) Synthesis and characterization of metal complexes of Cu (II), Ni (II), Zn (II), Co (II), Mn (II) and Cd (II) with tetradentate Schiff bases. Turk J Chem 30(1):41–48

    CAS  Google Scholar 

  41. Ma L, Li W, Zhu S, Wang L, Guan S (2021) Corrosion inhibition of Schiff bases for Mg-Zn-Y-Nd alloy in normal saline: experimental and theoretical investigations. Corros Sci 184:109268

    Article  CAS  Google Scholar 

  42. Mohanty P, Behura R, Bhardwaj V, Dash PP, Sahoo SK, Jali BR (2022) Recent advancement on chromo-fluorogenic sensing of aluminum (III) with Schiff bases. Trends Environ Anal Chem 34:e00166

    Article  CAS  Google Scholar 

  43. Hachem K, Jasim SA, Al-Gazally ME, Riadi Y, Yasin G, TurkiJalil A, DehnoKhalaji A (2022) Retracted: adsorption of Pb (II) and Cd (II) by magnetic chitosan-salicylaldehyde Schiff base: synthesis, characterization, thermal study and antibacterial activity. J Chin Chem Soc 69(3):512–521

    Article  CAS  Google Scholar 

  44. Abdel-Rahman LH, Abu-Dief AM, Atlam FM, Abdel-Mawgoud AH, Alothman AA, Alsalme AM, Nafady A (2020) Chemical, physical, and biological properties of Pd (II), V (IV) O, and Ag (I) complexes of N3 tridentate pyridine-based Schiff base ligand. J Coord Chem 73(23):3150–3173

    Article  CAS  Google Scholar 

  45. Kaczmarek MT, Zabiszak M, Nowak M, Jastrzab R (2018) Lanthanides: Schiff base complexes, applications in cancer diagnosis, therapy, and antibacterial activity. Coord Chem Rev 370:42–54

    Article  CAS  Google Scholar 

  46. Malik MA, Dar OA, Gull P, Wani MY, Hashmi AA (2018) Heterocyclic Schiff base transition metal complexes in antimicrobial and anticancer chemotherapy. MedChemComm 9(3):409–436

    Article  CAS  PubMed  Google Scholar 

  47. de Fátima Â, de Paula Pereira C, Olímpio CRSDG, de Freitas Oliveira BG, Franco LL, da Silva PHC (2018) Schiff bases and their metal complexes as urease inhibitors—a brief review. J Adv Res 13:113–126

    Article  PubMed  PubMed Central  Google Scholar 

  48. Almashal FA, Mohammed MQ, Hassan QMA, Emshary CA, Sultan HA, Dhumad AM (2020) Spectroscopic and thermal nonlinearity study of a Schiff base compound. Opt Mater 100:109703

    Article  CAS  Google Scholar 

  49. Al Zoubi W, Ko YG (2016) Organometallic complexes of Schiff bases: Recent progress in oxidation catalysis. J Organomet Chem 822:173–188

    Article  CAS  Google Scholar 

  50. Salama HE, Saad GR, Sabaa MW (2015) Synthesis, characterization and biological activity of Schiff bases based on chitosan and arylpyrazole moiety. Int J Biol Macromol 79:996–1003

    Article  CAS  PubMed  Google Scholar 

  51. Anush SM, Vishalakshi B, Kalluraya B, Manju N (2018) Synthesis of pyrazole-based Schiff bases of chitosan: evaluation of antimicrobial activity. Int J Biol Macromol 119:446–452

    Article  CAS  PubMed  Google Scholar 

  52. Das P, Linert W (2016) Schiff base-derived homogeneous and heterogeneous palladium catalysts for the Suzuki-Miyaura reaction. Coord Chem Rev 311:1–23

    Article  CAS  Google Scholar 

  53. Divya K, Pinto GM, Pinto AF (2017) Application of metal complexes of Schiff bases as an antimicrobial drug: a review of recent works. Int J Curr Pharm Res 9(3):27–30

    Article  CAS  Google Scholar 

  54. Gupta KC, Sutar AK (2008) Catalytic activities of Schiff base transition metal complexes. Coord Chem Rev 252(12–14):1420–1450

    Article  CAS  Google Scholar 

  55. Rana K, Pandurangan A, Singh N, Tiwari AK (2012) A systemic review of Schiff bases as an analgesic, anti-inflammatory. Int J Curr Pharm Res 4(2):5–11

    CAS  Google Scholar 

  56. Da Silva CM, da Silva DL, Modolo LV, Alves RB, de Resende MA, Martins CV, de Fátima  (2011) Schiff bases: a short review of their antimicrobial activities. J Adv Res 2(1):1–8

    Article  Google Scholar 

  57. Vigato PA, Tamburini S (2004) The challenge of cyclic and acyclic Schiff bases and related derivatives. Coord Chem Rev 248(17–20):1717–2128

    Article  CAS  Google Scholar 

  58. Kajal A, Bala S, Kamboj S, Sharma N, Saini V (2013) Schiff bases: a versatile pharmacophore. J Catal 2013:3512

    Google Scholar 

  59. Balouiri M, Sadiki M, Ibnsouda SK (2016) Methods for in vitro evaluating antimicrobial activity: a review. J Pharm Anal 6(2):71–79

    Article  PubMed  Google Scholar 

  60. Verma M, Pandeya SN, Singh KN, Stables JP (2004) Anticonvulsant activity of Schiff bases of isatin derivatives. Acta Pharm 54(1):49–56

    CAS  PubMed  Google Scholar 

  61. Azizian J, Mohammadi MK, Firuzi O, Razzaghi-asl N, Miri R (2012) Synthesis, biological activity and docking study of some new isatin Schiff base derivatives. Med Chem Res 21:3730–3740

    Article  CAS  Google Scholar 

  62. Xu Y, Shi Y, Lei F, Dai L (2020) A novel and green cellulose-based Schiff base-Cu (II) complex and its excellent antibacterial activity. Carbohydr Polym 230:115671

    Article  CAS  PubMed  Google Scholar 

  63. Hassan AS, Askar AA, Nossier ES, Naglah AM, Moustafa GO, Al-Omar MA (2019) Antibacterial evaluation, in silico characters and molecular docking of Schiff bases derived from 5-aminopyrazoles. Molecules 24(17):3130

    Article  PubMed  PubMed Central  Google Scholar 

  64. Ahmed A, Mushtaq I, Chinnam S (2023) Suzuki-Miyaura cross-couplings for alkyl boron reagent: recent developments—a review. Future J Pharm Sci 9(1):67

    Article  Google Scholar 

  65. GÜmÜŞ A, OkumuŞ V, GÜmÜŞ S (2020) Synthesis, biological evaluation of antioxidant-antibacterial activities and computational studies of novel anthracene- and pyrene-based Schiff base derivatives. Turk J Chem 44(4):1200–1215

    Article  PubMed  PubMed Central  Google Scholar 

  66. Jesmin M, Ali MM, Khanam JA (2010) Antitumour activities of some Schiff bases derived from benzoin, salicylaldehyde, amino phenol and 2,4 dinitrophenyl hydrazine. Thai J Pharm Sci 34(1):20–31

    CAS  Google Scholar 

  67. Makawana JA, Sangani CB, Lin L, Zhu HL (2014) Schiff’s base derivatives bearing nitroimidazole and quinoline nuclei: new class of anticancer agents and potential EGFR tyrosine kinase inhibitors. Bioorg Med Chem Lett 24(7):1734–1736

    Article  CAS  PubMed  Google Scholar 

  68. Zhang K, Wang P, Xuan LN, Fu XY, Jing F, Li S, Chen BQ (2014) Synthesis and antitumor activities of novel hybrid molecules containing 1,3,4-oxadiazole and 1,3,4-thiadiazole bearing Schiff base moiety. Bioorg Med Chem Lett 24(22):5154–5156

    Article  CAS  PubMed  Google Scholar 

  69. Chemchem M, Menacer R, Merabet N, Bouridane H, Yahiaoui S, Moussaoui S, Belkhiri L (2020) Green synthesis, antibacterial evaluation and QSAR analysis of some isatin Schiff bases. J Mol Struct 1208:127853

    Article  CAS  Google Scholar 

  70. Salihović M, Pazalja M, Halilović SŠ, Veljović E, Mahmutović-Dizdarević I, Roca S, Trifunović S (2021) Synthesis, characterization, antimicrobial activity and DFT study of some novel Schiff bases. J Mol Struct 1241:130670

    Article  Google Scholar 

  71. Mushtaq I, Ahmed A (2023) Synthesis of biologically active sulfonamide-based indole analogs: a review. Future J Pharm Sci 9(1):1–13

    Google Scholar 

  72. Aragón-Muriel A, Liscano Y, Upegui Y, Robledo SM, Ramírez-Apan MT, Morales-Morales D, Polo-Cerón D (2021) In vitro evaluation of the potential pharmacological activity and molecular targets of new benzimidazole-based Schiff base metal complexes. Antibiotics 10(6):728

    Article  PubMed  PubMed Central  Google Scholar 

  73. Chen Y, Mi Y, Li Q, Dong F, Guo Z (2020) Synthesis of Schiff bases modified inulin derivatives for potential antifungal and antioxidant applications. Int J Biol Macromol 143:714–723

    Article  CAS  PubMed  Google Scholar 

  74. Cheng LX, Tang JJ, Luo H, Jin XL, Dai F, Yang J, Zhou B (2010) Antioxidant and antiproliferative activities of hydroxyl-substituted Schiff bases. Bioorg Med Chem Lett 20(8):2417–2420

    Article  CAS  PubMed  Google Scholar 

  75. Devi P, Singh K, Kubavat B (2023) Synthesis, spectroscopic, quantum, thermal and kinetics, antibacterial and antifungal studies: Novel Schiff base 5-methyl-3-((5-bromosalicylidene) amino)-pyrazole and its transition metal complexes. Results Chem. 5:100813

    Article  CAS  Google Scholar 

  76. Ejidike IP (2018) Cu (II) Complexes of 4-[(1 E)-N-{2-[(Z)-Benzylidene-amino] ethyl} ethanimidoyl] benzene-1, 3-diol Schiff base: synthesis, spectroscopic, in-vitro antioxidant, antifungal and antibacterial studies. Molecules 23(7):1581

    Article  PubMed  PubMed Central  Google Scholar 

  77. Hamad A, Chen Y, Khan MA, Jamshidi S, Saeed N, Clifford M, Rahman KM (2021) Schiff bases of sulphonamides as a new class of antifungal agent against multidrug-resistant Candida auris. MicrobiologyOpen 10(4):e1218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Wei L, Zhang J, Tan W, Wang G, Li Q, Dong F, Guo Z (2021) Antifungal activity of double Schiff bases of chitosan derivatives bearing active halogeno-benzenes. Int J Biol Macromol 179:292–298

    Article  CAS  PubMed  Google Scholar 

  79. Al-Masoudi NA, Aziz NM, Mohammed AT (2009) Synthesis and In vitro anti-HIV activity of some new Schiff base ligands derived from 5-Amino-4-phenyl-4 H-1, 2, 4-triazole-3-thiol and their metal complexes. Phosphorus Sulfur Silicon 184(11):2891–2901

    Article  CAS  Google Scholar 

  80. Kumar KS, Ganguly S, Veerasamy R, De Clercq E (2010) Synthesis, antiviral activity and cytotoxicity evaluation of Schiff bases of some 2-phenyl quinazoline-4 (3) H-ones. Eur J Med Chem 45(11):5474–5479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Sriram D, Yogeeswari P, Myneedu NS, Saraswat V (2006) Abacavir prodrugs: microwave-assisted synthesis and their evaluation of anti-HIV activities. Bioorg Med Chem Lett 16(8):2127–2129

    Article  CAS  PubMed  Google Scholar 

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IM contributed to the design of the study and drafted the paper; AA contributed to drafting the paper and critical revision of the article; all authors have read and approved the final manuscript.

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Mushtaq, I., Ahmad, M., Saleem, M. et al. Pharmaceutical significance of Schiff bases: an overview. Futur J Pharm Sci 10, 16 (2024).

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