Synthesis and anti-HIV activity of a new isoxazole containing disubstituted 1,2,4-oxadiazoles analogs

[Display omitted] 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...

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Published in:Bioorganic & medicinal chemistry 2022-02, Vol.56, p.116612-116612, Article 116612
Main Authors: Kumar Kushwaha, Prem, Saurabh Srivastava, Kumar, Kumari, Neha, Kumar, Rajan, Mitra, Debashis, Sharon, Ashoke
Format: Article
Language:English
Subjects:
4-oxadiazoles
Anti-HIV Agents - chemical synthesis
Anti-HIV Agents - chemistry
Anti-HIV Agents - pharmacology
Bioisosteres
Cell Line
Dose-Response Relationship, Drug
HIV-1 - drug effects
HIV-1 inhibitors
Humans
Isoxazole-1
Isoxazoles - chemistry
Isoxazoles - pharmacology
Microbial Sensitivity Tests
Microwave irradiation
Molecular Structure
Oxadiazoles - chemical synthesis
Oxadiazoles - chemistry
Oxadiazoles - pharmacology
Structure-Activity Relationship
Virus Replication - drug effects
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Summary:[Display omitted] 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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2022.116612