In silico Docking Analysis of a Hydrazone Derivative of 2-Amino-4-Thiazoleacetic Acid Hydrazide as a Potential Antimalarial and Anticancer Agent | Chapter 01 | Chemistry and Biochemistry: Research Progress Vol. 8

 

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.

 

Author(s)details:-

 

Ngozi Patricia Ebosie
Department of Chemistry, Imo State University, Owerri, Nigeria.

 

Beniah Obinna Isiuku
Department of Chemistry, Imo State University, Owerri, Nigeria.

 

Pauline Amaka Nnagbo
Department of Microbiology, Imo State University, Owerri, Nigeria.

Please see the book here :- https://doi.org/10.9734/bpi/cbrp/v8/6281