Isoquinoline-based analogs of the cancer drug clinical candidate tipifarnib as anti-Trypanosoma cruzi agents.
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.
Chennamaneni
Naveen Kumar
NK
Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
Arif
Jenifer
J
Buckner
Frederick S
FS
Gelb
Michael H
MH
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
D000970:Antineoplastic Agents; D015363:Quinolones; D014344:Trypanocidal Agents; C402769:tipifarnib