Carbonic anhydrase inhibition and cytotoxicity studies of Mannich base derivatives of thymol

GÜL H. İ., Yamali C., Yasa A. T., Unluer E., Sakagami H., Tanc M., ...More

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, vol.31, no.6, pp.1375-1380, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 31 Issue: 6
  • Publication Date: 2016
  • Doi Number: 10.3109/14756366.2016.1140755
  • Journal Name: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1375-1380
  • Keywords: Carbonic anhydrase, cytotoxicity, Mannich bases, phenol, thymol, ANTICONVULSANT ACTIVITIES, OXIDATIVE STRESS, HYDROCHLORIDES, ACID
  • Çukurova University Affiliated: No

Abstract

Mannich bases of thymol were synthesized. The aminomethylation reaction was realised in the ortho position of the phenol for compounds 2 (dipropylamine), 3 (benzylamine), and 4 (dibenzylamine) while it was from para position for 1 (dimethylamine), 5 (piperidine), 6 (morpholine) and 7 (N-methylpiperazine). The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the compounds were asssessed against hCA I and hCA II. All compounds moderately inhibited hCA I and hCA II. The cytotoxicity of the compounds against four human oral squamous cell carcinoma cell lines were compared those against three normal oral cells. Tumor specificity values were about 2 or slightly more for the compounds 2, 3, 4, 5 and 6. Compound 2 showed cytostatic activity against OSCC cell lines at 16 to 32-fold lower concentrations as compared with normal cells. This suggests that compound 2 can be considered as cytotoxicity enhancing drug candidate for further investigations.