Synthesis and anti-HIV activity of a new isoxazole containing disubstituted 1, 2, 4-oxadiazoles analogs. (15th February 2022)

• Record Type: Journal Article
• Authors: Kumar Kushwaha, Prem; Saurabh Srivastava, Kumar; Kumari, Neha; Kumar, Rajan; Mitra, Debashis; Sharon, Ashoke
• Is Part Of: Bioorganic & medicinal chemistry. Volume 56(2022)
• Publication Date: 2022-02-15
• Subjects: Isoxazole-1 -- 2 -- 4-oxadiazoles -- Microwave irradiation -- HIV-1 inhibitors -- Bioisosteres; HNC Highest Non-cytotoxic Concentration -- GFP Green Fluorocence Protein -- HIV Human immunodeficiency virus -- AIDS Acquired immune deficiency syndrome -- cART Combination antiretroviral therapy -- HATU 2-(7-Aza-1H-benzotriazole-1-yl)-1, 1, 3, 3-tetramethyluronium hexafluorophosphate -- DIPEA Diisopropyl ethylamine -- DMF N, N-Dimethyl formamide -- NaHCO3 Sodium bicarbonate -- Na2CO3 Sodium carbonate -- S1P1 Sphingosine-1-phosphate receptor 1 -- CDI 1, 1′-carbonyldiimidazole -- EDC 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide -- ADME Absorption, Distribution, Metabolism and Excretion -- FDA Food and Drug Administration -- HDFs Host dependency factors -- CC50 50% cytotoxic concentration -- IC50 50% Inhibitory concentration -- CD4+ Cluster of Differentiation 4+ -- HSP90 Heat Shock Protein 90 -- NF-kB nuclear factor kappa-light-chain-enhancer of activated B cells -- LTR Long Terminal Repeat -- MDCK Madin Darby Canine Kidney -- ATP Adenosine Triphosphate -- gp120 Glycoprotein-120 -- DCC dicyclohexyl carbodiimide -- HRMS High Resolution Mass Spectrometry -- NMR Nuclear Magnetic Resonance -- IR Infrared spectroscopy -- UV Ultraviolet -- DMSO‑d6 Dimethylsulfoxide deuterated-6 -- MHz megahertz -- m. p melting point -- Hz hertz -- EtOAc Ethylacetate -- TLC Thin-layer chromatography -- EtOH Ethanol; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2022.116612
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Continuing on our antiviral drug discovery research, we intended to diversify our lead anti-HIV-1 inhibitor by non-classical isosteric replacement of amide to 1, 2, 4-oxadiazoles. The resulting molecules isoxazole-1, 2, 4-oxadiazole analogs were synthesized using mild bases in ethanol under microwave irradiation. The anti-HIV potential was checked in human CD4 + reporter cell lines, TZM-bl and CEM-GFP, at the highest non-cytotoxic concentration (HNC), demonstrating that 3-((3-(p-tolyl)isoxazol-5-yl)methyl)-1, 2, 4-oxadiazole and 3-((3-(4-chlorophenyl)isoxazol-5-yl)methyl)-1, 2, 4-oxadiazole inhibit HIV-1 replication significantly and could be considered as a new lead candidate against HIV-1.