Labdane analogs with o-quinol, catechol and hydroquinone moiety have been synthesized using Diels-Alder reaction of methyl 3,4-dioxocyclohexa-1,5-diene-carboxylate, 3,4-dioxocyclohexa-1,5-diene-carboxylic acid and 3,6-dioxocyclohexa-1,4-dienecarboxylic acid with mono terpene 1,3-dienes, namely ocimene and myrcene. The resulting molecules and their derivatives were evaluated for their anti-HIV-1 activity using TZM-bl cell based virus infectivity assay. Two molecules 13 and 18 showed anti-HIV activity with IC50 values 5.0 (TI=11) and 4.6 (TI=46)μM, respectively. The compounds 17, 18 and 20 showed efficacy against HIV-1 integrase activity and showed inhibition with IC50 13.4, 11.1 and 11.5μM, respectively. The HIV-1 integrase inhibition activity of these synthetic molecules was comparable with integric acid, the natural fungal metabolite. Molecular modeling studies for the HIV-1 integrase inhibition of these active synthetic molecules indicated the binding to the active site residues of the enzyme.
Keywords: 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide; ACN; Anti-HIV-1 activity; Computational study; Diels–Alder reaction; HIV-1 integrase inhibition; IBD; IN CCD; Labdane analogs; MTT; RT; TI; acetonitrile; integrase catalytic core domain; iodoso benzene diacetate; o-Quinol–catechol–hydroquinone moiety; room temperature; therapeutic index.
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