Novel hybrid isoindole-1,3(2H)-dione compounds containing a 1H-tetrazole moiety: Synthesis, biological evaluation, and molecular docking studies.


Tan A., Kizilkaya S., Noma S. A. A. , Ates B., Kara Y.

Journal of biochemical and molecular toxicology, vol.36, 2022 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 36
  • Publication Date: 2022
  • Doi Number: 10.1002/jbt.23015
  • Journal Name: Journal of biochemical and molecular toxicology
  • Journal Indexes: Science Citation Index Expanded, Scopus, Agricultural & Environmental Science Database, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE
  • Keywords: 1H-tetrazole, 3(2H)-dione, anhydrase isoenzymes (hCA I and II), hybrid molecules, isoindole-1, molecular docking, xanthine oxidase, CARBONIC-ANHYDRASE, INHIBITORY PROPERTIES, ANTICANCER ACTIVITY, URIC-ACID, DERIVATIVES, TETRAZOLE

Abstract

In this study, novel hybrid isoindole-1,3(2H)-dione compounds (10 and 11) carrying a 1H-tetrazole moiety were synthesized, characterized and their inhibitory properties against xanthine oxidase (XO) and carbonic anhydrase isoenzymes (hCA I and hCA II) were investigated. Allopurinol for XO and acetazolamide for carbonic anhydrase isoenzymes were used as positive standards in inhibition studies. In addition, compounds 8 and 9, which were obtained in the intermediate step, were also investigated for their inhibition effects against the three enzymes. According to the enzyme inhibition results, hybrid isoindole-1,3(2H)-dione derivatives 10 and 11 showed significant inhibitory effects against all three enzymes. Surprisingly, compound 8, containing a SCN functional group, exhibited a greater inhibitory effect than the other compounds against hCA I and hCA II. The IC50 values of compound 8 against hCA I and hCA II were found to be 3.698 +/- 0.079 and 3.147 +/- 0.083 mu M, respectively. Compound 8 (IC50 = 4.261 +/- 0.034 mu M) showed higher activity than allopurinol (IC50 = 4.678 +/- 0.029 mu M) and the other compounds against XO, as well. These results clearly show the effect of the SCN group on the inhibition. In addition, in silico molecular docking studies were performed to understand the molecular interactions between each compound and enzymes, and the results were evaluated.