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: Naveen Kumar Chennamaneni, Jenifer Arif, Frederick S Buckner, Michael H Gelb
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 19 Issue 23 Pg. 6582-4 (Dec 01 2009) ISSN: 1464-3405 [Electronic] England
• PMID: 19875282 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents
• Quinolones
• Trypanocidal Agents
• tipifarnib

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Chagas Disease (drug therapy)
• Drug Evaluation, Preclinical
• Mice
• Molecular Conformation
• Parasitic Sensitivity Tests
• Quinolones (chemical synthesis, chemistry, pharmacology)
• Stereoisomerism
• Structure-Activity Relationship
• Trypanocidal Agents (chemical synthesis, chemistry, pharmacology)
• Trypanosoma cruzi (drug effects, growth & development)