title: Synthesis, anti-HIV activity, integrase enzyme inhibition and molecular modeling of catechol, hydroquinone and quinol labdane analogs.
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 11.5μM, 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.
authors.affiliation: Laboratory for Advanced Research in Natural and Synthetic Chemistry, V.G. Vaze College, Mumbai University, Mithagar Road, Mulund (East), Mumbai 400 081, India.
authors.forename: Rohan
authors.initials: R
authors.lastname: Pawar
authors.affiliation: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India.
authors.forename: Tiyasa
authors.initials: T
authors.lastname: Das
authors.affiliation: Laboratory for Advanced Research in Natural and Synthetic Chemistry, V.G. Vaze College, Mumbai University, Mithagar Road, Mulund (East), Mumbai 400 081, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mishra
authors.affiliation: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India.
authors.lastname: Nutan
authors.affiliation: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India.
authors.forename: Boskey
authors.initials: B
authors.lastname: Pancholi
authors.affiliation: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India. Electronic address: skgupta@nii.ac.in.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: Laboratory for Advanced Research in Natural and Synthetic Chemistry, V.G. Vaze College, Mumbai University, Mithagar Road, Mulund (East), Mumbai 400 081, India. Electronic address: sujata8b@gmail.com.
authors.forename: Sujata V
authors.initials: SV
authors.lastname: Bhat
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002396:Catechols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006678:HIV / Q000187:drug effects* / Q000201:enzymology; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006873:Hydroquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D002396:Catechols; D019428:HIV Integrase Inhibitors; D006873:Hydroquinones; D019427:HIV Integrase; C034221:catechol; C031927:hydroquinone
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