title: Camptothecin-7-yl-methanthiole: semisynthesis and biological evaluation.
abstract: The introduction of a methylenthiol group at position 7 of camptothecin was carried out in four steps. This preparation also yielded the corresponding disulfide, which behaves as a prodrug due to its reactivity with glutathione. Assessment of their antiproliferative activities, investigations of their mechanism of action, and molecular modeling analysis indicated that the 7-modified camptothecin derivatives described herein maintain the biological activity and drug-target interactions of the parent compound.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Christodoulou
authors.forename: Franco
authors.initials: F
authors.lastname: Zunino
authors.forename: Valentina
authors.initials: V
authors.lastname: Zuco
authors.forename: Stella
authors.initials: S
authors.lastname: Borrelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Comi
authors.forename: Gabriele
authors.initials: G
authors.lastname: Fontana
authors.forename: Marisa
authors.initials: M
authors.lastname: Martinelli
authors.forename: James B
authors.initials: JB
authors.lastname: Lorens
authors.forename: Lasse
authors.initials: L
authors.lastname: Evensen
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sironi
authors.forename: Stefano
authors.initials: S
authors.lastname: Pieraccini
authors.forename: Lisa
authors.initials: L
authors.lastname: Dalla Via
authors.forename: Ornella Maria
authors.initials: OM
authors.lastname: Gia
authors.forename: Daniele
authors.initials: D
authors.lastname: Passarella
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D026942:DNA Topoisomerases / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011355:Prodrugs; D059004:Topoisomerase I Inhibitors; D026942:DNA Topoisomerases; D005978:Glutathione; D002166:Camptothecin