2. Academic Validation
  3. Synthesis of substituted phenanthrene-9-benzimidazole conjugates: Cytotoxicity evaluation and apoptosis inducing studies

Synthesis of substituted phenanthrene-9-benzimidazole conjugates: Cytotoxicity evaluation and apoptosis inducing studies

  • Eur J Med Chem. 2017 Nov 10:140:128-140. doi: 10.1016/j.ejmech.2017.09.006.
Niggula Praveen Kumar 1,  Pankaj Sharma 1,  S Sujana Kumari 2,  Umarani Brahma 2,  Shalini Nekkanti 1,  Nagula Shankaraiah 3,  Ahmed Kamal 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 2 Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 3 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar@niperhyd.ac.in.
  • 4 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: ahmedkamal@iict.res.in.
PMID: 28923381 DOI: 10.1016/j.ejmech.2017.09.006
Abstract

A series of new phenanthrene-9-benzimidazole conjugates has been synthesized by condensing phenanthrene aldehydes with various substituted o-phenylenediamines. The title compounds were evaluated for their in vitro cytotoxic potential against various human Cancer cell lines like breast (BT-549), prostate (PC-3 and DU145), triple negative breast Cancer (MDA-MB-453), and human colon Cancer (HCT-116 and HCT-15) cells. Among the tested compounds, 10o displayed significant in vitro cytotoxic activity against PC-3 prostate Cancer cells with an IC50 value of 6.32 ± 0.09 μM. Further, the cell cycle analysis indicated that it blocks G2/M phase of the cell cycle in a dose dependent manner. In order to determine the effect of the compound 10o on cell viability; phase contrast microscopy, AO/EB staining, DAPI staining, and DCFDA staining studies were performed. In these studies, apoptotic features were clearly observed indicating that the compound inhibited cell proliferation by Apoptosis. JC-1 staining and annexin binding assays indicated the extent of Apoptosis in PC-3 cells. Further, relative viscosity measurements and molecular docking studies indicated that these compounds bind to DNA by intercalation.

Keywords

Apoptosis; Benzimidazoles; Cytotoxicity; DNA interaction; Molecular modeling; Perkin condensation; Phenanthrene.

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