title: Structure-activity study and design of multidrug-resistant reversal compounds by a computer automated structure evaluation methodology.
abstract: We have studied the relation between the structure and the multidrug resistance-reversal activity of a set of diverse chemicals with the MULTICASE structure-activity program. A number of key structural features were identified as being related to multidrug resistance reversal activity. Using these key features, we identified seven new compounds predicted to have substantial activity. These were obtained and tested experimentally on a CHO/CHRC5 cell line derived from the AB1 Chinese hamster ovary line in the presence of vincristine and vinblastine. Of the seven compounds tested so far, four showed substantial reversal activity, the most potent of them exhibiting activity at par with verapamil.
authors.affiliation: Chemistry Department, Case Western Reserve University, Cleveland, Ohio 44106.
authors.forename: G
authors.initials: G
authors.lastname: Klopman
authors.forename: S
authors.initials: S
authors.lastname: Srivastava
authors.forename: I
authors.initials: I
authors.lastname: Kolossvary
authors.forename: R F
authors.initials: RF
authors.lastname: Epand
authors.forename: N
authors.initials: N
authors.lastname: Ahmed
authors.forename: R M
authors.initials: RM
authors.lastname: Epand
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D016206:Databases, Bibliographic; D015195:Drug Design; D004351:Drug Resistance / Q000502:physiology*; D004354:Drug Screening Assays, Antitumor; D015394:Molecular Structure; D012984:Software; D013329:Structure-Activity Relationship; D014747:Vinblastine / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014747:Vinblastine