2. Academic Validation
  3. Synthesis of podophyllotoxin linked β-carboline congeners as potential anticancer agents and DNA topoisomerase II inhibitors

Synthesis of podophyllotoxin linked β-carboline congeners as potential anticancer agents and DNA topoisomerase II inhibitors

  • Eur J Med Chem. 2018 Jan 20:144:557-571. doi: 10.1016/j.ejmech.2017.12.055.
Manda Sathish 1,  Botla Kavitha 2,  V Lakshma Nayak 1,  Yellaiah Tangella 1,  Ayyappan Ajitha 3,  Shalini Nekkanti 2,  Abdullah Alarifi 4,  Nagula Shankaraiah 5,  Narayana Nagesh 6,  Ahmed Kamal 7
Affiliations

Affiliations

  • 1 Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
  • 2 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 3 CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500 007, India.
  • 4 Catalytic Chemistry Research Chair, Chemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
  • 5 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar@niperhyd.ac.in.
  • 6 CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500 007, India. Electronic address: nagesh@ccmb.res.in.
  • 7 Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India; Catalytic Chemistry Research Chair, Chemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; School of Pharmaceutical Education and Research (SPER), Jamia Hamdad University, New Delhi 110 062, India. Electronic address: ahmedkamal@iict.res.in.
PMID: 29289881 DOI: 10.1016/j.ejmech.2017.12.055
Abstract

A series of new podophyllotoxin linked β-carboline congeners have been synthesized by coupling various substituted β-carboline acids with 4β-aminopodophyllotoxin. Evaluation of their Anticancer activity against a panel of human Cancer cell lines such as lung Cancer (A549), prostate Cancer (DU-145), MDA MB-231 (breast Cancer), HT-29 (colon Cancer) and HeLa (cervical Cancer) suggested that 7i and 7j are the most cytotoxic compounds with IC50 values of 1.07 ± 0.07 μM and 1.14 ± 0.16 respectively against DU-145 cell line. Further, detailed biological studies such as cell cycle analysis, Topoisomerase II inhibition, Comet assay, DNA binding studies and docking studies have revealed that these congeners are DNA interacting Topoisomerase II inhibitors.

Keywords

Cytotoxicity; Docking; Podophyllotoxin; Topoisomerase II inhibition; β-Carbolines.

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