A new bio-active asymmetric-Schiff base: synthesis and evaluation of calf thymus DNA interaction, topoisomerase II alpha inhibition, in vitro antiproliferative activity, SEM analysis and molecular docking studies


Yilmaz Z. K. , ÖZDEMİR Ö., ASLIM B., SULUDERE Z., Sahin E.

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2022 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2022
  • Doi Number: 10.1080/07391102.2022.2039297
  • Journal Name: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
  • Journal Indexes: Science Citation Index Expanded, Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Keywords: Schiff bases, CT-DNA, topoisomerase II, molecular docking, antiproliferative activity, cytokinesis-block micronucleus assay, scanning electron microscopy, COPPER(II) COMPLEXES, HISTONE DEACETYLASE, MEDICINAL CHEMISTRY, CRYSTAL-STRUCTURE, METAL-COMPLEXES, CANCER-CELLS, CU-II, CO II, BINDING, ACID

Abstract

In this paper, the asymmetric-Schiff base 2-(4-(2-hydroxybenzylideneamino)benzylideneamino)benzoic acid (SB-2) was newly synthesized and characterized by various spectroscopic methods. The interaction of SB-2 with calf thymus DNA was investigated by UV-vis, fluorescence spectroscopy and molecular docking methods. It was determined that SB-2 effectively binds to DNA via the intercalation mode. DNA electrophoretic mobility experiments displayed that topoisomerase II alpha could not cleave pBR322 plasmid DNA in the presence of SB-2, confirming that the Schiff base acts as a topo II suppressor. In the molecular docking studies, SB-2 was found to show an affinity for both the DNA-topoisomerase II alpha complex and the DNA. In vitro antiproliferative activity of SB-2 was screened against HT-29 (colorectal) and HeLa (cervical) human tumor cell lines by MTT assay. SB-2 diminished the cell viability in a concentration- and incubation time-dependent manner. The ability of SB-2 to measure DNA damage in tumor cells was evaluated with cytokinesis-block micronucleus assay after incubation 24 h and 48 h. Light and scanning electron microscopy experiments of tumor cells demonstrated an incubation time-dependent increase in the proportion of apoptotic cells (nuclear condensation and apoptotic bodies) suggesting that autophagy and apoptosis play a role in the death of cells. Based on the obtained results, it may be considered that SB-2 is a candidate for DNA-targeting antitumor drug. Communicated by Ramaswamy H. Sarma