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A series of new 2-(substitutedphenoxy)-N-[(aryl)methylidene]acetohydrazide analogues (8a-n) were synthesized in search of potential therapeutics for leishmaniasis. All the compounds were characterized by infrared (IR), nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. The compounds were further evaluated for in vitro antileishmanial activity against promastigotes of Leishmania donovani as per the standard protocol reported elsewhere. 2-(2,4-Dichlorophenoxy)-N′-{[4-(morpholin-4-yl)phenyl]methylidene}acetohydrazide (8k) showed the most promising antileishmanial activity with IC50 of 48.10 µM, free from cytotoxicity (>153.08 µM).