2. Academic Validation
  3. Design and synthesis of DNA-intercalative naphthalimide-benzothiazole/cinnamide derivatives: cytotoxicity evaluation and topoisomerase-IIα inhibition

Design and synthesis of DNA-intercalative naphthalimide-benzothiazole/cinnamide derivatives: cytotoxicity evaluation and topoisomerase-IIα inhibition

  • Medchemcomm. 2018 Nov 8;10(1):72-79. doi: 10.1039/c8md00395e.
N Sankara Rao 1 2,  Narayana Nagesh 3,  V Lakshma Nayak 1,  Satish Sunkari 1 2,  Ramya Tokala 4,  Gaddam Kiranmai 3,  Phanindranath Regur 3,  Nagula Shankaraiah 4,  Ahmed Kamal 1 2 5
Affiliations

Affiliations

  • 1 Medicinal Chemistry and Pharmacology , CSIR-Indian Institute of Chemical Technology , Hyderabad 500 007 , India . Email: ahmedkamal@iict.res.in.
  • 2 Academy of Scientific and Innovative Research. (AcSIR) , CSIR-Indian Institute of Chemical Technology , Hyderabad 500 007 , India.
  • 3 CSIR-Centre for Cellular and Molecular Biology , Hyderabad 500007 , India.
  • 4 Department of Medicinal Chemistry , National Institute of Pharmaceutical Education and Research (NIPER) , Hyderabad 500 037 , India . Email: shankar@niperhyd.ac.in.
  • 5 School of Pharmaceutical Education and Research , Jamia Hamdard , New Delhi , 110062 , India.
PMID: 30774856 DOI: 10.1039/c8md00395e
Abstract

A new series of different naphthalimide-benzothiazole/cinnamide derivatives were designed, synthesized and tested for their in vitro cytotoxicity on selected human Cancer cell lines. Among them, derivatives 4a and 4b with the 6-aminobenzothiazole ring and 5g with the cinnamide ring displayed potent cytotoxic activity against colon (IC50: 3.715 and 3.467 μM) and lung Cancer (IC50: 4.074 and 3.890 μM) cell lines when compared to amonafide (IC50: 5.459 and 7.762 μM). Later, the DNA binding studies for these selected derivatives (by CD, UV/vis, fluorescence spectroscopy, DNA viscosity, and molecular docking) suggested that these new derivatives significantly intercalate between two strands of DNA. In addition, the most potent derivatives 4a and 4b were also found to inhibit DNA topoisomerase-II.

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