Synthesis,anti-HIV activity,integrase enzyme inhibition and molecular modeling of catechol,hydroquinone and quinol labdane analogs |
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Institution: | 1. Department of Physics and Astronomy, Michigan State University, East Lansing, MI 48824, USA;2. Department of Biology and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, USA;3. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA |
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Abstract: | 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 11.5 μM, 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. |
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Keywords: | Labdane analogs Diels–Alder reaction Anti-HIV-1 activity Computational study HIV-1 integrase inhibition |
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