title: Anti-AIDS agents 87. New bio-isosteric dicamphanoyl-dihydropyranochromone (DCP) and dicamphanoyl-khellactone (DCK) analogues with potent anti-HIV activity.
abstract: Six 3'R,4'R-di-O-(S)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) and two 3'R,4'R-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives were designed, synthesized, and evaluated for inhibition of HIV-1(NL4-3) replication in TZM-bl cells. 2-Ethyl-2'-monomethyl-1'-oxa- and -1'-thia-DCP (5a, 6a), as well as 2-ethyl-1'-thia-DCP (7a) exhibited potent anti-HIV activity with EC(50) values of 30, 38 and 54 nM and therapeutic indexes of 152.6, 48.0 and 100.0, respectively, which were better than or comparable to those of the lead compound 2-ethyl-DCP in the same assay. 4-Methyl-1'-thia-DCK (8a) also showed significant inhibitory activity with an EC(50) of 128 nM and TI of 237.9.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Hong-Shan
authors.initials: HS
authors.lastname: Liu
authors.forename: Shi-Qing
authors.initials: SQ
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Cheng
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Xia
authors.forename: Keduo
authors.initials: K
authors.lastname: Qian
authors.forename: Yi
authors.initials: Y
authors.lastname: Xia
authors.forename: Zheng-Yu
authors.initials: ZY
authors.lastname: Yang
authors.forename: Chin-Ho
authors.initials: CH
authors.lastname: Chen
authors.forename: Susan L
authors.initials: SL
authors.lastname: Morris-Natschke
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002164:Camphor / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002867:Chromones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D006900:Hydroxylation; D020128:Inhibitory Concentration 50; D008214:Lymphocytes / Q000378:metabolism / Q000821:virology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
chemical_list: D019380:Anti-HIV Agents; D002867:Chromones; D003374:Coumarins; C543205:dihydropyranochromone; D002164:Camphor; C520900:khellactone