Affiliation: | 1. College of Natural Sciences, Department of Biological Sciences, Kongju National University, Gongju, 32588 South Korea;2. Department of Chemistry, Government College University, Lahore, 54000 Pakistan These two authors contributed equally to this study.;3. Department of Chemistry, Government College University, Lahore, 54000 Pakistan;4. The Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children's Hospital, Columbus, Ohio 43205 USA;5. Faculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Bandar Puncak Alam, 42300 Selangor, Malaysia Atta-ur-Rahman Institute for Natural Product Discovery (AuRIns), Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Bandar Puncak Alam, 42300 Selangor, Malaysia |
Abstract: | A multi-step synthesis of novel bi-heterocyclic N-arylated butanamides was consummated through a convergent strategy and the structures of these medicinal scaffolds, 7a–h , were corroborated using spectral techniques. The in vitro analysis of these hybrid molecules revealed their potent tyrosinase inhibition as compared to the standard used. The kinetics mechanism was investigated through Lineweaver-Burk plots which exposed that, 7f , inhibited tyrosinase enzyme non-competitively by forming the enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.025 μM. Their binding conformations were ascertained by in silico computational studies whereby these molecules disclosed good binding energy values (kcal/mol). So, it was anticipated from the current research that these bi-heterocyclic butanamides might be probed as imperative therapeutic agents for melanogenesis. |