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.

Background In medicinal chemistry, indole and its derivative play an important role. Indole is gaining a lot of importance in medicinal chemistry due to its physiological activity which includes anticancer, antitubercular, antimicrobial, antiviral, antimalarial, anti-inflammatory activities, antileishmanial agents, anti-cholinesterase, and enzyme inhibitory. The spread of antimicrobial resistance becomes a threat to both humans and animals. Antimicrobial resistance has been declared in the top 10 global major health risks by WHO including reported data of 2020 of AMR with 3,106,002 confirmed infections in humans across 70 countries. Result In this present work some new sulfonamide-based indole derivatives were synthesized by using 1H-indole -2 carboxylic acid as a starting material. The structure of all synthesized sulfonamide-based indole derivatives was confirmed by 1H NMR and LCMS Spectroscopy. Conclusion All the synthesized compounds were screened for anti-microbial activity against Gram Positive Staphylococcus aureus, Bacillus megaterium, and Gram Negative Klebsiella pneumonia, Escherichia coli, Salmonellatyphiae, Shigella sp., Enterobacter aerogenes. Among gram-positive Staphylococcus aureus, and Bacillus megaterium. The compound shows activity against Staphylococcus aureus, and among all gram-negative bacteria against Klebsiella pneumonia shows good activity.