Design, synthesis and molecular modelling studies of some pyrazole derivatives as carbonic anhydrase inhibitors

Dizdaroglu Y., ALBAY C., ARSLAN T., Ece A., Turkoglu E. A., Efe A., ...More

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, vol.35, no.1, pp.289-297, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 35 Issue: 1
  • Publication Date: 2020
  • Doi Number: 10.1080/14756366.2019.1695791
  • Journal Name: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, Food Science & Technology Abstracts, MEDLINE, Directory of Open Access Journals
  • Page Numbers: pp.289-297
  • Keywords: Pyrazole, carbonic anhydrase, molecular docking, ADME, ISOFORMS I, BIOLOGICAL EVALUATION, ISOZYMES I, HCA IX, DOCKING, ENZYME, POTENT, PURIFICATION, DISCOVERY, PROTEIN
  • Ondokuz Mayıs University Affiliated: Yes

Abstract

In this study, newly synthesised compounds 6, 8, 10 and other compounds (1-5, 7 and 9) and their inhibitory properties against the human isoforms hCA I and hCA II were reported for the first time. Compounds 1-10 showed effective inhibition profiles with K (I) values in the range of 5.13-16.9 nM for hCA I and of 11.77-67.39 nM against hCA II, respectively. Molecular docking studies were also performed with Glide XP to get insight into the inhibitory activity and to evaluate the binding modes of the synthesised compounds to hCA I and II. More rigorous binding energy calculations using MM-GBSA protocol which agreed well with observed activities were then performed to improve the docking scores. Results of in silico calculations showed that all compounds obey drug likeness properties. The new compounds reported here might be promising lead compounds for the development of new potent inhibitors as alternatives to classical hCA inhibitors.