title: Evaluation of HIV-1 inhibition by stereoisomers and analogues of the sesquiterpenoid hydroquinone peyssonol A.
abstract: Peyssonol A, a brominated natural product with documented anti-HIV-1 activity, was synthesized racemically along with 6 isomers and 15 truncated analogues and synthetic precursors. These compounds were screened in a cell-based assay against a recombinant HIV-1 strain to investigate structure-activity relationships. The results obtained suggest that both the aliphatic and aromatic domains of peyssonol A are responsible for its potency, while the stereochemical configuration of the substituents on the aliphatic domain, including their bromine atom, are largely irrelevant. Although none of the analogues tested were as potent as the parent natural product, several exhibited greater therapeutic indices due to reduced cytotoxicity, noting that nearly all compounds tested were measurably cytotoxic.
authors: Department of Chemistry, Columbia University, Havemeyer Hall, 3000 Broadway, New York, NY 10027, USA.
authors: Daniel S
authors: DS
authors: Treitler
authors: Zhufang
authors: Z
authors: Li
authors: Mark
authors: M
authors: Krystal
authors: Nicholas A
authors: NA
authors: Meanwell
authors: Scott A
authors: SA
authors: Snyder
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects*; D006873:Hydroquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D006873:Hydroquinones; D012717:Sesquiterpenes; C092045:peyssonol A