Synthesis, Molecular Docking, Pharmacokinetics, DFT Studies and Evaluation of Antibacterial and Antioxidant Activities of Acetamido thiazole Derivatives

Abstract

The heterocyclic fused ring of the aceteamide derivatives of thiazole have drawn a huge consideration owing to their expanded applications in the field of pharmaceutical chemistry. Thiazole derivatives (acetamido thiazole) reveal various medicinal properties such as analgestic, antiinflammatory, anticancer and antimicrobial activities. Various synthesis approaches leading to thiazoleacetamide scaffold have been reported such as, metal catalyzed reduction of p-nitroacetophenone, from 2-amino thiazole and phenyl deriveatives of 2-amino thiazole,. Currently, synthetic modification of acetamido thiazole derivatives at their 2 position of thiazole ring become an interesting approach to tune their biological properties in line with their applications. As a result, these classes of organic compounds become good candidate and play an important role towards medicinal chemistry. In present study, novel acetamido thiazole derivative (100b) was synthesized with 86% yield. The synthesized compounds were fully characterized mainly using NMR ( 1H-NMR, 13C-NMR and DEPT). Furthermore, the synthesized compounds were evaluated for their in vitro antibacterial activity against two Gram-negative bacterial strains (Escherichia coli, and Pseudomonas aurogonosa) and two Gram-positive bacteria (Streptococcus payogens and Staphylococcus aureus) by disk diffusion method. Among synthesized compounds, compound 100c and 100d showed medium inhibitory activity against Gram-positive, Staphylococcus aureus with 25±0.0 and 18 ± 2.82 mm zone of inhibition, respectively compared to standard drug Ceftazidime (13.5±0.707 mm) at 100 mg/mL. The radical scavenging activities of these compounds were evaluated using DPPH radical assay and of the synthesized compounds, compound 100c and 100b were showed the strongest activity with IC50 values of 1.67 and 1.59 μg/mL, respectively compared to the standard IC50 value of 1.57 μg/mL. The synthesized compounds were evaluated for their insilico molecular docking analysis using tyrosyl-tRNA synthetase because the antibacterial activity was higher on it and were found to have minimum binding energy. The drug likeness of the synthesized compound was performed and satisfies the Lipinski's rule of five with zero violations. In this study different bio-active acetamido thiazole derivatives were successfully synthesized and these compounds may serve as lead compound for further development of novel antibacterial and anticancer agents.