Affiliations 

  • 1 Department of Chemistry, Government College University, Lahore 54000, Pakistan
  • 2 Department of Chemistry, Government College University, Lahore 54000, Pakistan; College of Natural Sciences, Department of Biological Sciences, Kongju National University, Gongju 32588, South Korea. Electronic address: abbasi@gcu.edu.pk
  • 3 College of Natural Sciences, Department of Biological Sciences, Kongju National University, Gongju 32588, South Korea
  • 4 Faculty of Pharmacy and Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Level 9, FF3, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia
  • 5 Department of Chemistry, Government College University, Lahore 54000, Pakistan. Electronic address: dnalove@kongju.ac.kr
Bioorg Chem, 2019 05;86:197-209.
PMID: 30711702 DOI: 10.1016/j.bioorg.2019.01.040

Abstract

Keeping in mind the pharmacological importance of 2-aminothiazole and 1,2,4-triazole heterocyclic moieties, a series of novel ethylated bi-heterocyclic acetamide hybrids, 9a-p, was synthesized in a multi-step protocol. The structures of newly synthesized compounds were characterized by 1H NMR, 13C NMR, IR and EI-MS spectral studies. The inhibitory effects of these bi-heterocyclic acetamides (9a-n) were evaluated against elastase and all these molecules were identified as potent inhibitors relative to the standard used. The Kinetics mechanism was analyzed by Lineweaver-Burk plots which revealed that, 9h, inhibited elastase competitively by forming an enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.9 µM. The computational study was articulate with the experimental results and these ligands unveiled good binding energy values (kcal/mol). So, these molecules can be considered as promising medicinal scaffolds for the treatment of skin melanoma, wrinkle formation, uneven pigmentation, and solar elastosis.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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