Biological activity of bis-benzimidazole derivatives on DNA topoisomerase i and HeLa, MCF7 and A431 cells

A. Selcen Alpan, Sevil Zencir, I. Zupkó, Gunes Coban, B. Réthy, H. Semih Gunes, Zeki Topcu

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Benzimidazoles of both natural and synthetic sources are the key components of many bio-active compounds. Several reports have shown antifungal, antiviral, H2 receptor blocker and antitumor activities for benzimidazoles and their derivatives. In this study, we synthesized twelve bis-benzimidazole derivatives by selecting di(1H-benzo[d]imidazol-2-yl)methane as the main compound. The numbers of carbons at 2 positions of bis-benzimidazole derivatives were changed from 1 to 4, and derivatives were synthesized with methyl substitutions at 5- and/or 6- positions. The compounds were screened via in vitro plasmid superciol relaxation assays using mammalian DNA topoisomerase I and cytostatic assays were carried out against HeLa (cervix adenocarcinoma), MCF7 (breast adenocarcinoma) and A431 (skin epidermoid carcinoma) cells for selected derivatives. Our results suggest that the malonic acid derivatives of bis-benzimidazoles, namely, bis(5-methyl-1H-benzo[d]imidazol-2-yl)methane and bis(5,6-dimethyl-1H-benzo[d] imidazol-2-yl)methane, were remarkably active compounds in interfering with DNA topoisomerase I and the former compound was also found to be cytotoxic against MCF7 and A431 cells. The inhibitory effects obtained with these derivatives are significant as these compounds can be potential sources of anticancer agents.

Original languageEnglish
Pages (from-to)844-849
Number of pages6
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume24
Issue number3
DOIs
Publication statusPublished - 2009

Fingerprint

Type I DNA Topoisomerase
MCF-7 Cells
Methane
Benzimidazoles
Adenocarcinoma
Histamine H2 Receptors
Cytostatic Agents
Cervix Uteri
Antineoplastic Agents
Antiviral Agents
Squamous Cell Carcinoma
Breast
Plasmids
Carbon
Skin
bis-benzimidazole

Keywords

  • Bis-benzimidazoles
  • Cytotostaticity
  • DNA topoisomerase I

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Medicine(all)

Cite this

Biological activity of bis-benzimidazole derivatives on DNA topoisomerase i and HeLa, MCF7 and A431 cells. / Alpan, A. Selcen; Zencir, Sevil; Zupkó, I.; Coban, Gunes; Réthy, B.; Gunes, H. Semih; Topcu, Zeki.

In: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 24, No. 3, 2009, p. 844-849.

Research output: Contribution to journalArticle

Alpan, A. Selcen ; Zencir, Sevil ; Zupkó, I. ; Coban, Gunes ; Réthy, B. ; Gunes, H. Semih ; Topcu, Zeki. / Biological activity of bis-benzimidazole derivatives on DNA topoisomerase i and HeLa, MCF7 and A431 cells. In: Journal of Enzyme Inhibition and Medicinal Chemistry. 2009 ; Vol. 24, No. 3. pp. 844-849.
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