Synthesis and biological activity of pyrrolidine/piperidine substituted 3-amido-9-ethylcarbazole derivatives

Sirin S., Duyar H., ASLIM B., SEFEROĞLU Z.

JOURNAL OF MOLECULAR STRUCTURE, vol.1242, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1242
  • Publication Date: 2021
  • Doi Number: 10.1016/j.molstruc.2021.130687
  • Journal Name: JOURNAL OF MOLECULAR STRUCTURE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, INSPEC
  • Keywords: 3-Amido-9-ethylcarbazole, Acetylcholinesterase inhibition, Antioxidant activity, Antiproliferative effect, DNA damage, Topoisomerase II inhibition, DNA binding property, CARBAZOLE DERIVATIVES, ANTIOXIDANT ACTIVITY, DNA-BINDING, CANCER, COMPLEXES, INHIBITION, CHALCONES, DESIGN
  • Gazi University Affiliated: Yes

Abstract

In this study, pyrrolidine/piperidine substituted 3-amido-9-ethylcarbazole derivatives were synthesized and characterized by FT-IR, H-1 NMR, C-13 NMR spectroscopic and HRMS techniques. Acetylcholinesterase inhibition activity of the compounds were determined. Also, total antioxidant capacity, DPPH radical scavenging and metal chelating activity methods were used to evaluate the antioxidant effects of the compounds. In addition, the antiproliferative effect of the compounds on HT-29 and SH-SY5Y cells were assessed by the MTT assay. In addition, gel electrophoresis was utilized to determine DNA cleavage and topoisomerase II inhibition activities of 2a and 2b. Moreover, the features of the interaction between the compounds and calf thymus DNA (ct-DNA) were evaluated using UV-Vis absorption spectroscopic titration method. The biological activitiy demonstrated an acetylcholinesterase inhibition activity, antioxidant activity, and antiproliferative effect of the compounds on HT-29 and SH-SY5Y cells. The compounds also augmented DNA cleavage from the supercoiled form (SC, Form I) to the nicked circular form (NC, Form II), a process free of simultaneous Form III formation, which indicated the cleavage of single-strand DNA. The compounds prevented topoisomerase II functions at varying concentrations, and are connected to ct-DNA through the intercalation mode. Therefore, the compounds may be offered as anti-cancer drug candidate for use in cancer treatment. (C) 2021 Elsevier B.V. All rights reserved.