2. Academic Validation
  3. Synthesis and biological evaluation of pyrazole linked benzothiazole-β-naphthol derivatives as topoisomerase I inhibitors with DNA binding ability

Synthesis and biological evaluation of pyrazole linked benzothiazole-β-naphthol derivatives as topoisomerase I inhibitors with DNA binding ability

  • Bioorg Med Chem. 2019 Mar 1;27(5):708-720. doi: 10.1016/j.bmc.2019.01.011.
Burri Nagaraju 1,  Jeshma Kovvuri 1,  C Ganesh Kumar 2,  Sunitha Rani Routhu 3,  Md Adil Shareef 1,  Manasa Kadagathur 3,  Praveen Reddy Adiyala 3,  Sateesh Alavala 3,  Narayana Nagesh 4,  Ahmed Kamal 5
Affiliations

Affiliations

  • 1 Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Telangana, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India.
  • 2 Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Telangana, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India. Electronic address: cgkumar.iict@gov.in.
  • 3 Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Telangana, India.
  • 4 CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500007, Telangana, India. Electronic address: nagesh@ccmb.res.in.
  • 5 Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Telangana, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India; School of Pharmaceutical Education and Research, (SPER) Jamia Hamdard, New Delhi 110062, India. Electronic address: ahmedkamal915@gmail.com.
PMID: 30679134 DOI: 10.1016/j.bmc.2019.01.011
Abstract

A series of new pyrazole linked benzothiazole-β-naphthol derivatives were designed and synthesized using a simple, efficient and ecofriendly route under catalyst-free conditions in good to excellent yields. These derivatives were evaluated for their cytotoxicity on selected human Cancer cell lines. Among those, the derivatives 4j, 4k and 4l exhibited considerable cytotoxicity with IC50 values ranging between 4.63 and 5.54 µM against human cervical Cancer cells (HeLa). Structure activity relationship was elucidated by varying different substituents on benzothiazoles and pyrazoles. Further, flow cytometric analysis revealed that these derivatives induced cell cycle arrest in G2/M phase and spectroscopic studies such as UV-visible, fluorescence and circular dichroism studies showed that these derivatives exhibited good DNA binding affinity. Additionally, these derivatives can effectively inhibit the Topoisomerase I activity. Viscosity studies and molecular docking studies demonstrated that the derivatives bind with the minor groove of the DNA.

Keywords

Anticancer; Benzothiazole; Betanaphthol; DNA binding; Pyrazole; Topoisomerase.

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