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

Anil Kumar Verma; Abha Bishnoi; Shaheen Fatma; Huda Parveen; Vineeta Singh

doi:10.1055/s-0043-120660

Drug Research, Table of Contents

Drug Res (Stuttg) 2018; 68(04): 222-231
DOI: 10.1055/s-0043-120660

Original Article

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

Anil Kumar Verma

¹Department of Chemistry, University of Lucknow, Lucknow 226007, India

,

Abha Bishnoi

¹Department of Chemistry, University of Lucknow, Lucknow 226007, India

,

Shaheen Fatma

¹Department of Chemistry, University of Lucknow, Lucknow 226007, India

,

Huda Parveen

¹Department of Chemistry, University of Lucknow, Lucknow 226007, India

,

Vineeta Singh

²Department of Biotechnology, IET Lucknow 226021, India

› Author Affiliations

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 ¹H NMR, ¹³C 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.

Key words

Benzimidazole moiety - Mannich reaction - Molecular Docking

Full Text

References

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Supplementary Material

Supplementary Material