A brief review of the biological potential of indole derivatives

Various bioactive aromatic compounds containing the indole nucleus showed clinical and biological applications. Indole scaffold has been found in many of the important synthetic drug molecules which gave a valuable idea for treatment and binds with high affinity to the multiple receptors helpful in developing new useful derivatives. Indole derivatives possess various biological activities, i.e., antiviral, anti-inflammatory, anticancer, anti-HIV, antioxidant, antimicrobial, antitubercular, antidiabetic, antimalarial, anticholinesterase activities, etc. which created interest among researchers to synthesize a variety of indole derivatives. From the literature, it is revealed that indole derivatives have diverse biological activities and also have an immeasurable potential to be explored for newer therapeutic possibilities.


Background
Indole is also known as benzopyrrole which contains benzenoid nucleus and has 10 π-electrons (two from lone pair on nitrogen and double bonds provide eight electrons) which makes them aromatic in nature. Similar to the benzene ring, electrophilic substitution occurs readily on indole due to excessive π-electrons delocalization [1]. Indole is an important heterocyclic system that provides the skeleton to lysergic acid diethylamide (LSD), strychnine, and alkaloid obtained from plants. Physically, they are crystalline colorless in nature with specific odors. The addition of the indole nucleus to medicinal compounds that is biologically active pharmacophore made it an important heterocyclic compound having broad-spectrum biological activities [2]. Due to this, researchers took interest to synthesize various scaffolds of indole for screening different pharmacological activities. Various natural compounds contain indole as parent nucleus for example tryptophan. Indole-3-acetic acid is a plant hormone produced by the degradation of tryptophan in higher plants. Derivatives of indole are of wide interest because of their diverse biological and clinical applications. Here, we have tried to summarize the important pharmacological activity of indole derivatives [3].
Indole-based spirothiazolidinones also have antiviral activity as discussed by Cihan-Üstündağ et al. Compounds presented inhibitory action in Vero cells against yellow fever and Punta Toro virus. The range of IC 50 values was 1.9-12 μM. (20) was the most active [12].

Anticancer activity
N-1 and C-3 substituted indole derivatives also showed cytotoxic properties as reported by Choppara et (58) were found to be cytotoxic [34].

Anti-HIV activity
N-arylsulfonyl-3-acetylindole derivative was prepared and evaluated as HIV-1 inhibitors analogs by Ran et al. (68) were the most effective against the anti-HIV-1 activity. SAR showed that acetyl group derivatives were more active [38].
Derivatives holding indole core exhibit different biological activities namely antidiabetic, anticancer, antimicrobial, anti-HIV, antiviral, anti-inflammatory, antioxidant, anticholinesterase, antitubercular, and antimalarial activities, etc. Due to these activities, indole has attracted the attention of researchers in the discovery of novel chemical entities. These chemical entities may be safer and effective drugs for various ailments. Summarizing the literature reports described above, we can say that indole displays a diverse spectrum of biological activities. Indole has an immense potential to be investigated for newer therapeutic possibilities. Chemistry of indole derivatives described in this review would help the researchers worldwide in the design and synthesis of novel drugs useful in the mitigation of various disorders.