Antiparasitic Evaluation and In Silico Investigation of New Acyl Hydrazones from 3-Iodo-5-methoxy-4-propargyloxybenzaldehyde

Ibrahim S. Al Nasr, Waleed S. Koko, Tariq A. Khan, Ismail Daoud, Ridha Ben Said, Noureddine Amdouni, Rainer Schobert, Bernhard Biersack

Abstract


Background: Potent and affordable antiparasitic drugs are required to meet current health problems caused by protozoal infectious diseases. 3-Iodo-5-methoxy-4-propargyloxyphenyl compounds are promising antiparasitic compounds.

Methods: Ten new and structurally simple acyl hydrazones were prepared from 3-iodo-5-methoxy-4-propargyloxybenzaldehyde and analyzed. Their activities against Toxoplasma gondii and Leishmania major parasites were evaluated and compared with their toxic effects on host cells. ADMET calculations as well as docking of the most promising derivatives in tubulin were performed.

Results: Promising antiparasitic effects and selectivities were discovered for certain acyl hydrazones. A new 3-fluorobenzoyl hydrazone was found highly active against T. gondii parasites yet weakly toxic to macrophages. Docking calculations suggest tubulin as a possible target. Moderate activities were observed for various compounds against L. major promastigotes. The relatively low toxicities observed for several compounds in macrophages indicate promising selectivity profiles. ADMET (absorption, distribution, metabolism, excretion and toxicity) calculations supported the drug-like properties of the most active compounds.

Conclusion: A new 3-fuorobenzoyl hydrazone from 3-iodo-5-methoxy-4-propargyloxybenzaldehyde with promising activity against Toxoplasma gondii was identified. The strong selectivity for Toxoplasma parasites can pave the way for the development of improved antitoxoplasmal drug candidates in the future. Certain toxic effects on kidney cells might require further structural modifications of the drug candidates.

Keywords: Acyl hydrazones; Alkynes; Neglected tropical diseases; Leishmaniasis; Toxoplasmosis; Drug discovery


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DOI: http://dx.doi.org/10.62940/als.v12i4.3671

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