Synthesis of new 1,2,4-triazole–(thio)semicarbazide hybrid molecules: Their tyrosinase inhibitor activities and molecular docking analysis

Gultekin E., BEKİRCAN O., KOLCUOĞLU Y., AKDEMİR A.

Archiv der Pharmazie, cilt.354, sa.8, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 354 Sayı: 8
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1002/ardp.202100058
  • Dergi Adı: Archiv der Pharmazie
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: 1,2,4-triazoles, 1,2,4-triazole-3-ones, biochemical kinetics, molecular docking, semicarbazides, thiosemicarbazides, tyrosinase inhibition
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

© 2021 Deutsche Pharmazeutische GesellschaftTyrosinase inhibition is very important in controlling melanin synthesis. If melanin synthesis is not controlled in metabolism, an unwanted increase in melanin synthesis occurs. As melanin plays a role in the formation of skin color, its unusual levels cause some skin disorders such as pregnancy scars, age spots, and especially skin cancer (melanoma). However, the tyrosinase activity is also related to Parkinson's disease and some neurodegenerative diseases. For all these reasons, the medicinal as well as the cosmetic industries focus on research on tyrosinase inhibitors for the treatment of skin disorders and some neurodegenerative diseases. In this study, 32 new 1,2,4-triazole–(thio)semicarbazide hybrid molecules (6a–p and 7a–p) were synthesized, starting from 4-amino-1-pentyl-3-phenyl-1H-1,2,4-triazole-5(4H)-one. These compounds were evaluated for their inhibitory activity against mushroom tyrosinase. The results indicated that 6h, 6m, 6n, and 6p exhibited the most effective inhibitory activity, with IC50 values of 0.00162 ± 0.0109, 0.00166 ± 0.0217, 0.00165 ± 0.019, and 0.00197 ± 0.0063 μM, respectively, compared with kojic acid as the reference drug (IC50 = 14.09 ± 0.02 μM). Also, molecular docking analyses were performed to suggest possible binding poses for the ligands. As a result, derivatives 6h, 6m, 6n, and 6p can be used as promising tyrosinase inhibitor candidates in the medicinal, cosmetics, or food industries.