1,3,4-oxadiazole derivatives as potential antimicrobial agents.

Due to the emergence of drug-resistant microbial strains, different research groups are continuously developing novel drug molecules against already exploited and unexploited targets. 1,3,4-Oxadiazole derivatives exhibited noteworthy antimicrobial activities. The presence of 1,3,4-oxadiazole moiety in antimicrobial agents can modify their polarity and flexibility, which significantly improves biological activities due to various bonded and non-bonded interactions viz. hydrogen bond, steric, electrostatic, and hydrophobic with target sites. The present review elaborates the therapeutic targets and mode of interaction of 1,3,4-oxadiazoles as antimicrobial agents. 1,3,4-oxadiazole derivatives target enoyl reductase (InhA), 14α-demethylase in the mycobacterial cell; GlcN-6-P synthase, thymidylate synthase, peptide deformylase, RNA polymerase, dehydrosqualene synthase in bacterial strains; ergosterol biosynthesis pathway, P450-14α demethylase, protein-N-myristoyltransferase in fungal strains; FtsZ protein, interfere with purine and functional protein synthesis in plant bacteria. The present review also summarizes the effect of different moieties and functional groups on the antimicrobial activity of 1,3,4-oxadiazole derivatives.

A review on synthetic account of 1,2,4-oxadiazoles as anti-infective agents.

Most of the currently marketed drugs consist of heterocyclic scaffolds containing nitrogen and or oxygen as heteroatoms in their structures. Several research groups have synthesized diversely substituted 1,2,4-oxadiazoles as anti-infective agents having anti-bacterial, anti-viral, anti-leishmanial, etc. activities. For the first time, the present review article will provide the coverage of synthetic account of 1,2,4-oxadiazoles as anti-infective agents along with their potential for SAR, activity potential, promising target for mode of action. The efforts have been made to provide the chemical intuitions to the reader to design new chemical entity with potential of anti-infective activity. This review will mark the impact as the valuable, comprehensive and pioneered work along with the library of synthetic strategies for the organic and medicinal chemists for further refinement of 1,2,4-oxadiazole as anti-infective agents.

CoViTris2020 and ChloViD2020: a striking new hope in COVID-19 therapy.

Designing anticoronavirus disease 2019 (anti-COVID-19) agents is the primary concern of medicinal chemists/drug designers nowadays. Repurposing of known active compounds against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new effective and time-saving trend in anti-COVID-19 drug discovery. Thorough inhibition of the coronaviral-2 proteins (i.e., multitarget inhibition) is a possible powerful favorable strategy for developing effectively potent drugs for COVID-19. In this new research study, I succeeded to repurpose the two antioxidant polyhydroxy-1,3,4-oxadiazole compounds CoViTris2020 and ChloViD2020 as the first multitarget coronaviral protein blockers with extremely higher potencies (reach about 65 and 304 times, for CoViTris2020, and 20 and 93 times, for ChloViD2020, more potent than remdesivir and favipiravir, respectively). These two 2,5-disubstituted-1,3,4-oxadiazoles were computationally studied (through molecular docking in almost all SARS-CoV-2 proteins) and biologically assessed (through a newly established robust in vitro anti-COVID-19 assay) for their anticoronaviral-2 bioactivities. The data obtained from the docking investigation showed that both ligands promisingly exhibited very strong inhibitory binding affinities with almost all docked enzymes (e.g., they displayed extremely lower binding energies of - 12.00 and - 9.60 kcal/mol, respectively, with the SARS-CoV-2 RNA-dependent RNA polymerase "RdRp"). The results of the biological assay revealed that CoViTris2020 and ChloViD2020 significantly displayed very high anti-COVID-19 activities (anti-SARS-CoV-2 EC50 = 0.31 and 1.01 µM, respectively). Further in vivo/clinical studies for the development of CoViTris2020 and ChloViD2020 as anti-COVID-19 medications are required. In brief, the ascent of CoViTris2020 and ChloViD2020 as the two lead members of the novel family of anti-COVID-19 polyphenolic 2,5-disubstituted-1,3,4-oxadiazole derivatives represents a promising hope in COVID-19 therapy. CoViTris2020 and ChloViD2020 inhibit SARS-CoV-2 life cycle with surprising EC50 values of 0.31 and 1.01 µM, respectively. CoViTris2020 strongly inhibits coronaviral-2 RdRp with exceptionally lower inhibitory binding energy of - 12.00 kcal/mol.