title: Synthesis and preliminary in vitro biological evaluation of 7α-testosterone-chlorambucil hybrid designed for the treatment of prostate cancer.
abstract: The synthesis of 7α-testosterone-chlorambucil hybrid is reported. This compound is made from testosterone in a 6 step reaction sequence and with 23% overall yield. An alternative convergent reaction sequence yielded the same hybrid through a Grubbs metathesis reaction between chlorambucil allyl ester and 7α-allyltestosterone with 35% overall yield. MTT assays showed that the hybrid is selective towards hormone-dependent prostate cancer cell line (LNCaP (AR+)) and shows similar activity than the parent drug, chlorambucil. Thus, the new hybrid shows promising potential for drug targeting of hormone-dependent prostate cancer through its capacity of delivering chlorambucil directly to the site of treatment. This could extend the use of chlorambucil to prostate cancer in the future.
authors.affiliation: Département de Chimie et Physique, Université du Québec à Trois-Rivières, C.P. 500, Trois-Rivières, Québec, Canada G9A 5H7. Electronic address: Dominic.Bastien@uqtr.ca.
authors.forename: Dominic
authors.initials: D
authors.lastname: Bastien
authors.forename: Rana
authors.initials: R
authors.lastname: Hanna
authors.forename: Valérie
authors.initials: V
authors.lastname: Leblanc
authors.forename: Éric
authors.initials: É
authors.lastname: Asselin
authors.forename: Gervais
authors.initials: G
authors.lastname: Bérubé
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002699:Chlorambucil / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D008968:Molecular Conformation; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D002699:Chlorambucil; D013739:Testosterone