Synthesis and evaluation of lipase inhibitory activities of substituted 1,2,4-triazole derivatives

Ozdemir Y., BEKİRCAN O., ÇOLAK A., DOKUZPARMAK Ç.

INDIAN JOURNAL OF CHEMISTRY SECTION B-ORGANIC CHEMISTRY INCLUDING MEDICINAL CHEMISTRY, cilt.59, sa.9, ss.1409-1417, 2020 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 59 Sayı: 9
  • Basım Tarihi: 2020
  • Dergi Adı: INDIAN JOURNAL OF CHEMISTRY SECTION B-ORGANIC CHEMISTRY INCLUDING MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Sayfa Sayıları: ss.1409-1417
  • Anahtar Kelimeler: 1,2,4-Triazoles, acetohydrazide derivatives, lipase inhibitory activities, molecular modeling, PANCREATIC LIPASE, HETEROCYCLIC-COMPOUNDS, ALPHA-GLUCOSIDASE, BIOLOGICAL EVALUATION, ORLISTAT, OBESITY, DRUGS, EFFICACY, DOCKING, AMYLASE
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

Pancreatic lipase (PL) plays a major role in the hydrolysis of dietary triglycerides to monoglycerides and free fatty acids in the small intestine before absorption of fats. The excessive consumption of dietary fat (triglyceride) and not to utilize it for energy production can cause an increase in obesity. Obesity is one of the serious health problem in the world and leads to many diseases such as some types of cancer, heart disease, gallstones, sleep apnea, fatty liver disease, type-2 diabetes, hypertension, coronary artery disease. Therefore, lipase is the target enzyme to prevent these diseases and the inhibitors of lipase are very important molecules as drug candidate molecules. In this study, fifteen new heterocyclic compounds have been synthesized starting from 2-[3-(4-chlorobenzyl)-5-(4-chlorophenyl)-1H-1,2,4-triazol-4-yl]-acetohydrazide and their anti-lipase activities have been examined. According to in vitro inhibition studies, molecule 2e is found to be the most potent inhibitor with the lowest IC50 value. Docking studies' results have substantially supported this result and it is seen that compound 2e is one of the four molecules with the highest binding affinity. This molecule binds to the enzyme in its binding pocket by means of weak interactions with mainly Ile79, Asp80, Val260, Arg257 and His264.