Discovery of Novel Thiazol-2-Amines and Their Analogues as Bioactive Molecules: Design, Synthesis, Docking and Biological Evaluation

Abstract

A simple and highly efficient procedure for the synthesis of novel thiazol-2-amines, via Mannich reaction with secondary amines, is described. The newly synthesized derivatives 8(A-E): and 9(A-E): were characterized by H NMR,C NMR, IR, Mass spectroscopy and elemental analysis. All the derivatives were evaluated for their in-vitro anti-microbial activity against a panel of pathogenic strains of bacteria and fungi. The SAR showed that the secondary amines had a significant impact on the in-vitro antimicrobial activity of this class of agents. The most potent analogue N-((1H-benzo[d]imidazol-1-yl)methyl)-N-(2(trifluoromethyl)phenyl)-4,5-dihydrothiazol-2-amine (8C): showed excellent inhibition with MIC (zoi) 6.25 (22.5), 25 (21.5) and 25 (18) µg/mL against E. coli, S. typhi and P. aeruginosa respectively as compared to the standard drug. Molecular docking results suggest that compound exhibited inhibitory activity by binding of the title compound within the active sites of the inhibiting Enoyl ACP reductase, Lipid A, Pyridoxal kinase and type I DHQase enzymes. The compound exhibited promising anti-microbial activity which can be further explored as potential lead for the development of cheaper, safe, effective and potent drugs against resistant microbial parasites.

Thiamine‐dependent regulation of mammalian brain pyridoxal kinase in vitro and in vivo

“…Finally, we revealed selectivity of the thiamine‐dependent regulation of hPdxK, compared with another PLP‐producing enzyme, hPNPO. Interestingly, a recent study has shown that derivatives of thiazol, one of the thiamine constituents, are PdxK inhibitors of potential pharmacological importance (Verma et al, 2018). Physiological relevance of our results is further supported by an evolutionary relationship between thiamine diphosphokinase and PdxK, that is, the vitamin kinases generating the coenzyme forms of the vitamins B 1 and B 6 (Castro‐Fernandez et al, 2014).…”