Synthesis and evaluation of novel chromanone and quinolinone analogues of uniflorol as anti-leishmanial agents

Abstract

Within this work, we describe the design and synthesis of a range of novel chromanones and quinolinones, based on natural products reported to possess anti-leishmanial action. The core heterocycles were obtained either via classical or ionic liquid mediated Kabbe condensation in the case of chromanones, or aqueous Sonogashira based alkynylation followed by acid-catalysed cyclisation in the case of quinolinones. Upon testing in promastigotes, axenic amastigotes and Leishmania-infected macrophages, compound 13c was identified as displaying interesting activity, inhibiting axenic amastigotes and intracellular amastigotes with IC50s of 25.3 and 24.6μM respectively.

Keywords

• Natural product chemistry
• Organic chemistry
• Pharmaceutical chemistry
• Chromanone
• Quinolinone
• Leishmania