title: Plant-derived and semi-synthetic calanolide compounds with in vitro activity against both human immunodeficiency virus type 1 and human cytomegalovirus.
abstract: Plant-derived and semi-synthetic calanolide compounds with anti-human immunodeficiency virus type 1 (HIV-1) activity were tested for anti-human cytomegalovirus (HCMV) activity in both cytopathic effect inhibition and plaque reduction assays. The results indicated that the anti-HCMV activity of calanolide compounds does not correlate with their activity against HIV-1. The semi-synthetic 12-keto derivatives tended to be more active against HCMV than the corresponding 12-OH congeners, which were more active against HIV-1. It appeared that the 7,8-unsaturated double bond in the chromene ring played a certain role in maintaining activities against both HCMV and HIV-1. Saturation of the double bond increased the EC50 values against both viruses, with concomitant increase in toxicity. The calanolide compounds reported here are the first non-nucleoside analogues capable of inhibiting both HIV-1 and HCMV and, therefore, may be useful chemoprophylactic agents for HCMV in HIV-infected people or vice versa.
authors.affiliation: MediChem Research and Sarawak MediChem Pharmaceuticals, Lemont, IL 60439, USA. zxu@mcr.medichem.com
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Xu
authors.forename: E R
authors.initials: ER
authors.lastname: Kern
authors.forename: L
authors.initials: L
authors.lastname: Westbrook
authors.forename: L B
authors.initials: LB
authors.lastname: Allen
authors.forename: R W
authors.initials: RW
authors.lastname: Buckheit
authors.forename: C K
authors.initials: CK
authors.lastname: Tseng
authors.forename: T
authors.initials: T
authors.lastname: Jenta
authors.forename: M T
authors.initials: MT
authors.lastname: Flavin
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D003374:Coumarins / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D006801:Humans; D008826:Microbial Sensitivity Tests; D039681:Pyranocoumarins; D010948:Viral Plaque Assay
chemical_list: D019380:Anti-HIV Agents; D003374:Coumarins; D039681:Pyranocoumarins; C075959:calanolide A