A large number of novel chromenochalcones were synthesized by pyridine-catalysed chromenylation of mono-chelated meta-dihydric acetophenones with the monoterpene, citral dimethyl acetal and subsequent Claisen–Schmidt condensation of the resultant acylchromenes with appropriate aromatic aldehydes. These chromenochalcones 1–19 were screened against in vitro extracellular promastigotes and intracellular amastigotes of Leishmania donovani. The most potent compound in this series was compound 9 with a pyridine ring-A, which showed 99% inhibition of promastigotes at 10μg/ml, 82% at 0.25μg/ml and 96% at 10μg/ml concentration against amastigotes.