title: Cyclopentenylcytosine. A carbocyclic nucleoside with antitumor and antiviral properties.
abstract: Cyclopentenylcytosine (CPE-C, 2), a pyrimidine analogue of the fermentation derived carbocyclic nucleoside neplanocin A, has been synthesized from the optically active cyclopentenylamine 3b by two synthetic routes. CPE-C demonstrates significant antitumor activity against both the sensitive and ara-C resistant lines of L1210 leukemia in vivo. Multiple long term survivors are produced in both tumor models. The compound also gives 100% growth inhibition of the solid human A549 lung and MX-1 mammary tumor xenografts grown in athymic mice. Good activity is also observed against a third human tumor xenograft model, metastatic LOX melanoma. CPE-C has significant activity against both DNA and RNA viruses in vitro. Potent activity is observed against HSV-1 (TK+ and TK-), HSV-2, vaccinia, cytomegalovirus, and varicella-zoster virus. Good activity is also found against a strain of influenza virus (Hong Kong flu), vesicular stomatitis virus, Japanese encephalitis virus, and Punta Toro virus.
authors.affiliation: Laboratory of Medicinal Chemistry, National Cancer Institute, Bethesda, Maryland 20892.
authors.forename: V E
authors.initials: VE
authors.lastname: Marquez
authors.forename: M I
authors.initials: MI
authors.lastname: Lim
authors.forename: S P
authors.initials: SP
authors.lastname: Treanor
authors.forename: J
authors.initials: J
authors.lastname: Plowman
authors.forename: M A
authors.initials: MA
authors.lastname: Priest
authors.forename: A
authors.initials: A
authors.lastname: Markovac
authors.forename: M S
authors.initials: MS
authors.lastname: Khan
authors.forename: B
authors.initials: B
authors.lastname: Kaskar
authors.forename: J S
authors.initials: JS
authors.lastname: Driscoll
mesh_terms: D015092:3-Deazauridine / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D055598:Chemical Phenomena; D002621:Chemistry; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004267:DNA Viruses / Q000187:drug effects; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009975:Orthomyxoviridae / Q000187:drug effects; D012328:RNA Viruses / Q000187:drug effects; D012513:Sarcoma, Experimental / Q000188:drug therapy; D014780:Viruses / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D015092:3-Deazauridine; D003562:Cytidine; C045911:cyclopentenyl cytosine