Medicinal Perspective of Indole Derivatives: Recent Developments and Structure-Activity Relationship Studies

Abstract

: Heterocyclic compounds play significant role in various biological processes of human body and many of them are in clinical use due to their diverse, chemical and biological properties. Among these, indole is one of most promising pharmacologically active molecules. Due to its chemical reactivity, indole has been willingly modified to obtain a variety of new lead molecules, which has been successfully utilized to obtained novel drug candidates for the treatment of different pharmacological diseases. Indole-based compounds such as vincristine (Anticancer), reserpine (Antihypertensive), amedalin (Antidepressant) and many more describe the medicinal and pharmacological importance of the indole in uplifting human life. In this review, we compiled various reports on indole derivatives from 2015 onwards and their biological significance including antifungal, antiprotozoal, antiplatelet, anti-Alzheimer’s, anti-Parkinson’s, antioxidant and anticancer potential. In addition, structure activity relationship studies of the different derivatives have been included. We have also discussed novel synthetic strategies developed during this period for the synthesis of different indole derivatives. We believe this review article will provide comprehensive knowledge about the medicinal importance of indoles and will help in the design and synthesis of novel indole-based molecules with high potency and efficacy.

Recent investigations into synthesis and pharmacological activities of phenoxy acetamide and its derivatives (chalcone, indole and quinoline) as possible therapeutic candidates

“…Due to the presence of an electron-rich pyrrole moiety [141,142], that can use non-covalent interactions with various other molecules through hydrogen bonding formation between NH moiety and π-π system [143]. Because of this ideal property, indole and its diverse derivatives are widely used for the design and development of novel drugs [144]. A broad range of pharmacological applications has Scheme 18 Synthesis of two new series of indole derivatives Scheme Synthesis of indole hydrazone derivative been linked to natural and artificial molecules that hold an indole nucleus, providing it an appropriate building block for several therapeutic agents [145].…”

“…Quinoline-based Schiff base derivatives (144) have been introduced by Muhammad Taha et al [188] by refluxing methanolic mixture of methyl quinoline-6-carboxylate (142) and hydrazine hydrate for 6 h to obtain quinoline-6-carbohydarzide (143). The intermediate ( 143) was then refluxed for 3 h with various aromatic aldehydes in the presence of 5-6 drops of glacial acetic acid to obtain quinoline derivatives (Z)-N'-ethylidenequinoline-6-carbohydrazide (144) as shown in Scheme 24.…”

Piperazine, a Key Substructure for Antidepressants: Its Role in Developments and Structure‐Activity Relationships

“…Piperazine core is well‐known to play an important role in balancing the pharmacokinetic profile of designed compounds. Due to this innate quality, since long it has been used in the development of various classes of pharmacologically active compounds including anthelmintic, [23] antioxidant, [24] antimicrobial, [25,26] anti‐HIV, [27,28] antiviral, [29,30] anti‐inflammatory, [31,32] cognition enhancer, [33] metal chelators, [34] anti‐Parkinson's, [35] antidiabetic, [36] antimalarial, [37,38] antidepressant, [39,40] anti‐Alzheimer's, [41–43] antitubercular, [44] antiplasmodial, [45] etc. There are several drug molecules in clinical use which contain piperazine pharmacophore in its structural features (Table 1).…”

Synthesis, comparativein vitroantibacterial, antioxidant and UV fluorescence studies of bis indole Schiff bases and molecular docking with ct‐DNA and SARS‐CoV‐2 Mpro

“…[ 3,4 ] The indole nucleus has time and again been proved to have a variety of biological applications such as antibacterial, antitumor, anticonvulsant, and antihypertensive activity. [ 5–8 ] However, bis‐indole compounds have shown high antibacterial activities against many antibiotic resistant strains. [ 9 ]…”