2. Academic Validation
  3. Design, synthesis and biological evaluation of new β-carboline-bisindole compounds as DNA binding, photocleavage agents and topoisomerase I inhibitors

Design, synthesis and biological evaluation of new β-carboline-bisindole compounds as DNA binding, photocleavage agents and topoisomerase I inhibitors

  • Eur J Med Chem. 2018 Jan 1:143:1563-1577. doi: 10.1016/j.ejmech.2017.10.054.
Jeshma Kovvuri 1,  Burri Nagaraju 1,  V Lakshma Nayak 2,  Ravikumar Akunuri 3,  M P Narasimha Rao 2,  Ayyappan Ajitha 4,  Narayan Nagesh 5,  Ahmed Kamal 6
Affiliations

Affiliations

  • 1 Academy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India; Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 2 Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 3 National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 4 Centre for Cellular and Molecular Biology, Hyderabad 500007, India.
  • 5 Centre for Cellular and Molecular Biology, Hyderabad 500007, India. Electronic address: nagesh5112@gmail.com.
  • 6 Academy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India; Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India; School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi 110062, India. Electronic address: ahmedkamal@iict.res.in.
PMID: 29129513 DOI: 10.1016/j.ejmech.2017.10.054
Abstract

A series of new β-carboline-bisindole compounds were designed, synthesized and evaluated for their antiproliferative activity against human Cancer cell lines, such as A549 (lung Cancer), DU-145 (prostate Cancer), HeLa (cervical Cancer) and MCF-7 (breast Cancer). All the compounds exhibited considerable antiproliferative activity. Among them, compounds 7g and 7r exhibited significant antiproliferative activity against DU-145 cells with IC50 values 1.86 and 1.80 μM respectively. Further, these compounds effectively inhibit DNA Topoisomerase I activity and can also cleave the pBR322 plasmid upon irradiation with UV light. In addition, Annexin V-FITC assay suggested that these compounds induced Apoptosis in DU- 145 cell line (prostate Cancer). To know the binding mode of these compounds with DNA, spectroscopic studies were also carried out. These new compounds were showing a unique mode of binding with DNA, both biophysical studies such as UV-Visible, fluorescence, circular dichroism and molecular docking studies revealed that the β-carboline-bisindole compounds exhibit combilexin type of interaction with DNA.

Keywords

Antiproliferative activity; Bis-indole; DNA-binding affinity; Photocleavage; Topoisomerase I; β-Carboline.

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