Molecular Docking, ADME Evaluation and Synthesis of Thiourea Derivatives and Their Metal Complexes as Potential Antibacterial Agents

B.S., Mominn (2025) Molecular Docking, ADME Evaluation and Synthesis of Thiourea Derivatives and Their Metal Complexes as Potential Antibacterial Agents. Masters thesis, Universiti Malaysia Sarawak.

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Abstract

Antibacterial resistance has become a major threat worldwide. Due to lack of discovery of new antibiotics and increasing cases of resistance, there is an urgent need to discover novel classes of antibiotics with improved activity and less toxicity with the help of computational tools. Twelve amino acid bearing thiourea compounds had been docked using AutoDock Vina 1.5.6 against DNA Gyrase Enzyme (PDB ID: 1KZN) and pharmacologically evaluated using SwissADME software to look for potential antimicrobial agent. The cinnamoyl derivatives (compound 1-3) demonstrated high docking scores between -5.7 and 7.1 kJ/mol along with good pharmacokinetic profiles with the adherence to the Lipinski’s Rule of Five. Subsequently, the docking of Cu(II), Zn(II) and Co(II) complexes of compound 1-3 recorded higher docking scores between -6.9 and -8.3 kJ/mol compared to its free ligand despite violation of the Lipinski’s Rule. Thus, compound 1-3 and its complexes were selected for synthesis. The formation of compound 1-3 was confirmed by the presence of NH and C=S groups at 3165 – 3056 cm-1 and 1293 – 1269 cm-1 respectively, based on Fourier Transform Infrared (FTIR) spectra as well as -CONH and -CSNH signals at δH 11.4 - 11.2 ppm from 1H Nuclear Magnetic Resonance (NMR) data. The formation of complexes were confirmed by the shifting of C=O of the carboxylate group at 1731-1716 cm-1 to a lower frequency. The biological evaluation of compound 1-3 and complexes 1a-3c against E. coli ATCC 25922 strain by agar well method indicated that compound 2, complex 1a and 2a were potentially active antimicrobial agents with inhibition zone 11 – 13 mm. This study offers a computer-driven discovery of novel thiourea compound and its complexes as antibacterial agent.

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