Molecular Insights into Coumarin Analogues as Antimicrobial Agents: Recent Developments in Drug Discovery

Abstract

A major global health risk has been witnessed with the development of drug-resistant bacteria and multidrug-resistant pathogens linked to significant mortality. Coumarins are heterocyclic compounds belonging to the benzophenone class enriched in different plants. Coumarins and their derivatives have a wide range of biological activity, including antibacterial, anticoagulant, antioxidant, anti-inflammatory, antiviral, antitumour, and enzyme inhibitory effects. In the past few years, attempts have been reported towards the optimization, synthesis, and evaluation of novel coumarin analogues as antimicrobial agents. Several coumarin-based antibiotic hybrids have been developed, and the majority of them were reported to exhibit potential antibacterial effects. In the present work, studies reported from 2016 to 2020 about antimicrobial coumarin analogues are the focus. The diverse biological spectrum of coumarins can be attributed to their free radical scavenging abilities. In addition to various synthetic strategies developed, some of the structural features include a heterocyclic ring with electron-withdrawing/donating groups conjugated with the coumarin nucleus. The suggested structure−activity relationship (SAR) can provide insight into how coumarin hybrids can be rationally improved against multidrug-resistant bacteria. The present work demonstrates molecular insights for coumarin derivatives having antimicrobial properties from the recent past. The detailed SAR outcomes will benefit towards leading optimization during the discovery and development of novel antimicrobial therapeutics.

4-Methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin

“…Its derivatives have found broad applications such as fluorescent probes [1][2][3][4], food additives [5][6][7], in polymer chemistry [8][9][10][11], and so on. Numerous representatives have displayed variable bioactivity profiles [12][13][14][15][16][17][18], including anticancer [19][20][21][22][23][24], anti inflammatory [25][26][27], anti-tuberculosis [28,29], antimicrobial [30], and many others. Several drugs with coumarin skeleton are available on the market, such as immunosuppressant scoparone, anti-inflammatory drug 8-methoxypsoralen, vasodilator carbochromen, anticoagulants warfarin and phenprocoumon, antifungal agent osthole, anti-HIV preparatus calanolide, anticancer drug flavopiridol, antibiotics novobiocin and clorobiocin, and so on; some are shown in Figure 1.…”

Cytogenotoxicity assessment of 3‐(3,4‐dihydroxyphenyl)‐7,8‐dihydroxycoumarin on HepG2/C3A cells and leukocytes

“…Bibliographic references describe natural coumarins and their synthetic derivatives exhibiting pharmacological activities as anticancer, antioxidant, anti-inflammatory, vasorelaxant, antimicrobial, antiviral, and enzymatic inhibition (Bhattarai et al, 2021;Cheke et al, 2022;Li et al, 2021;Matos et al, 2011Matos et al, , 2012Matos et al, , 2016Viña, Matos, Ferino, et al, 2012). Modulation of the coumarin scaffold, in particular the introduction of hydroxyl groups, may allow obtaining chemical entities with antioxidant effects, interesting in the treatment of several chronic diseases (Garg et al, 2020;Guardado-Yordi et al, 2017;Viña, Matos, Yáñez, et al, 2012).…”

Formulation and Evaluation of Gastroretentive Floating Microspheres loaded with Lamivudine

“…As per the literature assessment, different dosages for Lamivudine were available [13][14][15][16][17][18] . Also, some floating systems were reported for Lamivudine 19 .…”