In silico Docking Analysis of a Hydrazone Derivative of 2-Amino-4-Thiazoleacetic Acid Hydrazide as a Potential Antimalarial and Anticancer Agent

Abstract

Hydrazide-hydrazones have recently gained great importance due to their diverse biological properties, including anti-inflammatory, antibacterial, antifungal, antituberculosis, antimalarial and anticonvulsant activities. This study aimed to synthesise and characterise a hydrazone compound (ATAPH) and to evaluate its in silico potential as an antimalarial and anticancer agent by investigating its interactions with selected protein targets. 2-amino-4-thiazoleacetic acid hydrazide (ATAH) was prepared from the reaction of ethyl-2-amino-4-thiazoleacetate with hydrazine hydrate. The hydrazone derivative, 2-(2-amino-1,3-thiazol-4-yl)-N'-[(E)-(4-methoxyphenyl)methylidene]acetohydrazide (ATAPH) was synthesised by the condensation reaction of 2-amino-4-thiazoleacetic acid hydrazide (ATAH) with 4-methoxybenzaldehyde. The synthesised compounds were characterised using spectro-analytical methods. The in silico docking studies of the synthesized compounds were performed against some antimalarial targets; P. falciparum lactase dehydrogenase (PfLDH) (PDB ID: 1U5A), P. falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) (PDB ID: 3UM8), P. falciparum dihydrorotate dehydrogenase (PfDHODH) (PDB ID: 6I55) and some anticancer targets; Epidermal Growth Factor Receptor (EGFR) (PDB ID: 3POZ), and Selective Androgen Receptor Modulator (SARM) (PDB ID: 3V49). The oral bioavailability and drug-like properties of the compounds were determined using the Lipinski rule of 5 (RO5). ATAH has a molecular weight of 172.21, 3 hydrogen bond donors (HBD), 3 hydrogen bond acceptors (HBA) and log P of –0.58. ATAPH has a molecular weight of 290.34, 2 hydrogen bond donors (HBD), 4 hydrogen bond acceptors (HBA) and log P of 1.61, indicating favourable drug-like characteristics. The in silico docking studies revealed that the antimalarial activity was higher than the anticancer activity. ATAPH exhibited better binding affinity compared to ATAH, indicating its potential as a promising antimalarial and anticancer agent. The physicochemical properties revealed the drug-likeness ability of the compounds. Further in vitro and in vivo analysis of these compounds should be carried out to validate these findings.