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 Biochemistry, University of Agriculture, Faisalabad 38040, Pakistan
  • 6 College of Natural Sciences, Department of Biological Sciences, Kongju National University, Gongju 32588, South Korea. Electronic address: dnalove@kongju.ac.kr
Bioorg Chem, 2019 05;86:459-472.
PMID: 30772647 DOI: 10.1016/j.bioorg.2019.01.036

Abstract

The present research was designed for the selective synthesis of novel bi-heterocyclic acetamides, 9a-n, and their tyrosinase inhibition to overwhelm the problem of melanogenesis. The structures of newly synthesized compounds were confirmed by spectral techniques such as 1H NMR, 13C NMR, and EI-MS along with elemental analysis. The inhibitory effects of these bi-heterocyclic acetamides (9a-n) were evaluated against tyrosinase and all these molecules were recognized as potent inhibitors relative to the standard used. The Kinetics mechanism was analyzed by Lineweaver-Burk plots which explored that compound, 9h, inhibited tyrosinase competitively by forming an enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.0027 µM. The computational study was coherent with the experimental records and these ligands exhibited good binding energy values (kcal/mol). The hemolytic analysis revealed their mild cytotoxicity towards red blood cell membranes and hence, these molecules can be pondered as nontoxic medicinal scaffolds for skin pigmentation and related disorders.

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

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