A Review of the Therapeutic Importance of Indole Scaffold in Drug Discovery

Abstract

Indole is known as a versatile heterocyclic building block for its multiple pharmacological activities and has a high probability of success in the race for drug candidates. Many natural products, alkaloids, and bioactive heterocycles contain indole as the active principle pharmacophore. These encourage the researchers to explore it as a lead in the drug development process. The current manuscript will serve as a torchbearer for understanding the structurally diverse class of indole derivatives with extensive pharmacological activity. The current manuscript describes the intermediates and their functional groups responsible for superior biological activity compared to the standard. The review is written to help researchers to choose leads against their target but also to provide crucial insight into the design of a hybrid pharmacophore-based approach in drug design with enhanced potential. The present reviews on the indole derivatives correlate the structures with biological activities as well as essential pharmacophores, which were highlighted. The discussion was explored under challenging targets like dengue, chikungunya (anti-viral), antihypertensive, diuretic, immunomodulator, CNS stimulant, antihyperlipidemic, antiarrhythmic, anti-Alzheimer’s, and neuroprotective, along with anticancer, antitubercular, antimicrobial, anti-HIV, antimalarial, anti-inflammatory, antileishmanial, anti-anthelmintic, and enzyme inhibitors. So, this review includes a discussion of 19 different pharmacological targets for indole derivatives that could be utilized to derive extensive information needed for ligand-based drug design. The article will guide the researchers in the selection, design of lead and pharmacophore, and ligand-based drug design using indole moiety.

Platinum(IV) Prodrugs Incorporating an Indole-Based Derivative, 5-Benzyloxyindole-3-Acetic Acid in the Axial Position Exhibit Prominent Anticancer Activity

“…We hypothesised that P-5B3A, 5-5B3A and 56-5B3A would produce higher levels of ROS than their equivalent platinum(II) precursors (PHENSS, 5MESS and 56MESS) and platinum(IV) scaffolds (PHENSS(IV)(OH) 2 , 5MESS(IV)(OH) 2 and 56MESS(IV)(OH) 2 ) because of the coordinated 5B3A axial ligand. The indole core of 5B3A has garnered synthetic interest because of the numerous pharmacological potencies it offers [52,53,55], and one of them is the generation of ROS [91,92].…”

“…With the vast number of bioactive ligands available to coordinate to platinum(IV), the indole-based derivative, 5-benzyloxyindole-3-acetic acid (5B3A) caught our interest. We have selected 5B3A as axial ligand because it incorporates an indole pharmacophore, which has been used in drug design and discovery [52,53]. The bicyclic nature of the compound exhibits multiple therapeutic properties [54,55]; and for this reason, it is found in many drugs, specifically those that target cancer [56].…”

Synthesis of N-substituted heterocycles in a sealed Monowave 50 reactor

“…Another nucleophile used was indole. It is known as a versatile heterocyclic building block due to its multiple pharmacological activities, and is often used in the creation of drug products candidates [21][22]. DMFA was used as solvent and potassium carbonate as base for the reaction of substance 1 with indole.…”

Selective Synthesis of 3-(1H-Tetrazol-5-yl)-indoles from 2H-Azirines and Arynes

“…Among the functionalized indoles, 2- and 3-substituted indoles have attracted much attention from organic and medicinal chemists as valuable building blocks for the synthesis of more complex molecules with biological activity. , Also, several indole-2 and 3-carboxylic acid derivatives as well as tetrazolyl-substituted indole derivatives have shown to possess promising biological activities. , In recent years, we have been exploring the carboxylic acid/tetrazole bioisosterism as a way of finding new molecules with potential biological activity. , …”