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Table 1 Correlation between the type of substitution and the exerted mechanism of action

From: Versatile mechanisms of 2-substituted benzimidazoles in targeted cancer therapy

Type of substitution Mechanism of action References
1-CH3
2-Aliphatic acid derivative
5- Nitrogen mustard
Alkylating agent [31, 32]
1,2-fused
5-Amide
6- CH3
Alkylating agent [33]
2-Acridine DNA binding agent [34]
2-Aromatic
6-Oxindole
DNA binding agent [35]
Head to tail bisbenzimidazole
5-Aromatic/piperazine
DNA binding agent [36]
1-Aromatic
2-Aromatic
5-Ester
DNA binding agent [37]
1,2-Fused DNA binding agent [38-40]
Cu complex with tetrabenzimidazoles DNA binding agent [41]
2-Indole
4-Aromatic
Tubulin inhibitor [45]
2-Pyrazole
6-Aliphatic/halogen
Tubulin inhibitor [46]
2-Carbamate
5-Se connector/indole
Tubulin inhibitor [47]
2-Urea
5-O-linker-Aromatic
Tubulin inhibitor [48]
2-Aromatic
4-H/OH/CH3
Tubulin inhibitor [49]
1-Aromatic ketone
2-Aromatic
Tubulin inhibitor [50]
1,2-Aromatic
5-Ester
Sirtuin 1&2 inhibitor [56]
2-Piperidine
4-Carboxamide
Poly (ADP-ribose) polymerase inhibitor [58]
2-Aromatic
4- Carboxamide
5/6-Halogen
Poly (ADP-ribose) polymerase inhibitor [59, 60]
2-Aromatic
3,4-Fused
Poly (ADP-ribose) polymerase inhibitor [61]
2-CH2-OH
5-NO2
Methionine synthase inhibitors [63]
2-Aromatic amide
5-NO2
Methionine synthase inhibitors [64]
1-Aromatic
2-CH3
6-Triazine
DHFR inhibitor [67]
1-Aromatic
2-CH3
6-Hetero-aromatic
DHFR inhibitor [68]
2-Aromatic Topoisomerase I&II inhibitors [71, 72]
2-Aromatic
4-Ester
Topoisomerase I&II inhibitors [73]
Head to tail bisbenzimidazole
2-Aromatic
5-piperazine
Topoisomerase I&II inhibitors [74,75]
Cu comlex
2-Pyridine
5-COOH
Topoisomerase I&II inhibitors [76]
1-Aromatic
2-C=O
3-Aliphatic
5-NO2
Androgen receptor antagonistic activity [78]
1-Aromatic
2-Aliphatic
5, 6-Halogen
Androgen receptor antagonistic activity [79]
2-Aromatic
5,6-Aliphatic
α-glucosidase inhibitors [82]
1,2-Aromatic
5-Amide
G9a Histone Methyltransferase inhibitors [85]
1-Hetero-aromatic
2-Aromatic
Pyruvate kinase inhibitors [88]
Head to Head bisbenzimidazoles
2-Hetero-aromatic connector
6-Piperazine
Telomerazse inhibitors [89]
Tribenzimidazoles
2-Aromatic
6-Piperazine
Telomerazse inhibitors [90]
5,6-Fused
2-Cyclic amine/piperazine
Telomerazse inhibitors [91]
2-Aromatic VEGFR-2 inhibitor [98]
2-Aromatic
6-Quinoline
VEGFR-2 inhibitor [92]
1-Aromatic
2-Furan
VEGFR-2 inhibitor [99]
1-Amide/Heteroaromatic
2-Furan
VEGFR-2 inhibitor [100]
2-Amide
5,6-Aliphatic
VEGFR-2 inhibitor [101]
2-Oxadiazole EGFR inhibitors [107]
1-Aliphatic amine
2-Amide
6-Halogen
EGFR inhibitors [108]
2-Indazole
5-Piperazine
FGFR1 inhibitors [110]
2-Aromatic ketone
6-Aliphatic
FGFR1 inhibitors [111]
2-Pyrrolopyrimidine
5-Sulfonyl/urea
Tie-2 receptor tyrosine kinase inhibitors [95]
2-Aromatic
5, 6-Aliphatic
Heparanase inhibitors [114]
2-Aromatic COX1&2 inhibitors [117]
2-Pyrazole
5-Aliphatic amine
Aurora A/B kinase inhibitors [120]
2-NH-aromatic
5-CF3
Aurora A/B kinase inhibitors [121]
2-Pyrazole
5-Morpholine
Aurora A/B kinase inhibitors [122]
1,2-Aliphatic
5-Hetero-aromatic
Aurora A/B kinase inhibitors [123]
2-Hetero-aromatic Checkpoint kinase (Chk1&Chk2) inhibitors [127]
2-Hetero-aromatic Checkpoint kinase (Chk1&Chk2) inhibitors [128]
2-Aromatic
5-Amide
Checkpoint kinase (Chk1&Chk2) inhibitors [129]
2-Aromatic
5-COOH/Amide
Checkpoint kinase (Chk1&Chk2) inhibitors [130]
2-CH3
5-Pyrazole
Checkpoint kinase (Chk1&Chk2) inhibitors [131]
2-Aliphatic amines/CF3
4,5,6,7-Halogen
Protein kinase rhCK2α inhibitor [135, 136]
2- CF3
4,5,6,7-Halogen
Protein kinase rhCK2α inhibitor [137]
2- CH3
4,5,6,7-Halogen
Protein kinase rhCK2α inhibitor [138]
2-Pyrazolo-pyridine
4-Aliphatic
Cyclin-dependant kinase (CDK) inhibitors [140]
2-Hetero-aromatic
4-Morpholine
7-Aliphatic
Insulin-like growth factor receptor-1 (IFG-1R) inhibitors [144]
1-Triazine
2-Halogen
Allosteric Mitogen-Activated Protein Kinase (MEK1) and Phosphatidylinositol 3-Kinase (PI3K) inhibitors [147]
2-Hetero-aromatic allosteric Mitogen-Activated Protein Kinase (MEK1) and Phosphatidylinositol 3-Kinase (PI3K) inhibitors [148]
1,2-Aromatic Farnesyl binding pocket of PDEδ inhibitor [141]
1-Triazine
2-CHF2
3-O-linker
Farnesyl binding pocket of PDEδ inhibitor [143]
2-Aromatic
6-Quinazolin
Dual c-Met and VEGFR-2 inhibitors [145]
2-Hetero-aromatic
6-Piperazine
Multi-target receptor tyrosine kinase inhibitors [147]
2-Pyrole
6-Amide
Multi-target receptor tyrosine kinase inhibitors [148]
2-Pyrazine
6-Aliphatic amine
Multi-target receptor tyrosine kinase inhibitors [149]
1-Aliphatic
2-Aromatic amine
Multi-target receptor tyrosine kinase inhibitors [149]