title: Isoquinoline-based analogs of the cancer drug clinical candidate tipifarnib as anti-Trypanosoma cruzi agents.
abstract: We developed a synthetic route to prepare isoquinoline analogs of the cancer drug clinical candidate tipifarnib. We show that these compounds kill Trypanosoma cruzi amastigotes grown in mammalian host cells at concentrations in the low nanomolar range. These isoquinolines represent new leads for the development of drugs to treat Chagas disease.
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: Naveen Kumar
authors.initials: NK
authors.lastname: Chennamaneni
authors.forename: Jenifer
authors.initials: J
authors.lastname: Arif
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Buckner
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014355:Chagas Disease / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D051379:Mice; D008968:Molecular Conformation; D021261:Parasitic Sensitivity Tests; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000970:Antineoplastic Agents; D015363:Quinolones; D014344:Trypanocidal Agents; C402769:tipifarnib