Preliminary in vitro evaluation of anti-leukemic and antimalarial activities of pyrrolo[1,2-a]quinoxaline-carboxylic acid hydrazone derivatives.

New pyrrolo[1,2-a]quinoxaline-2-carboxylic acid hydrazone derivatives were synthesized from nitroaniline using a multi-step pathway. Structure characterization of these novel substituted pyrrolo[1,2-a]quinoxaline-carboxylic acid hydrazones was achieved by using FT-IR, 1H NMR, 13C NMR, X-Ray and HRMS spectral analysis. These pyrroloquinoxaline hydrazone compounds were then evaluated in vitro for their potential on the human acute myeloid leukemia cell line MV4-11, in which (N'-pyridin-2-ylmethylene)pyrrolo[1,2-a]quinoxaline-2-carboxylic acid hydrazone 1a showed an IC50 value of 15.51 µM. Given the structural similarities between our hydrazone derivatives 1 and some recently published quinoline-type hydrazone compounds for antimalarial use, our compounds were also evaluated for their antimalarial activity. Among them, compound 1c demonstrated promising antiplasmodial activity, with an IC50 of 0.02 μM against the 3D7 strain of Plasmodium falciparum, exhibiting a selectivity index (SI) exceeding 5000 against this strain. Against the chloroquine-resistant Plasmodium falciparum W2 strain, hydrazone 1e emerged as the most potent and promising antimalarial candidate (IC50 = 0.03 mM), demonstrating a cytotoxicity to-antiprotozoal activity ratio exceeding 3333.