2. Academic Validation
  3. Rational design and synthesis of 2-anilinopyridinyl-benzothiazole Schiff bases as antimitotic agents

Rational design and synthesis of 2-anilinopyridinyl-benzothiazole Schiff bases as antimitotic agents

  • Bioorg Med Chem Lett. 2017 Jun 1;27(11):2549-2558. doi: 10.1016/j.bmcl.2017.03.089.
Thokhir B Shaik 1,  S M Ali Hussaini 2,  V Lakshma Nayak 2,  M Lakshmi Sucharitha 3,  M Shaheer Malik 2,  Ahmed Kamal 4
Affiliations

Affiliations

  • 1 Medicinal Chemistry and Pharmacology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500 007, India; Department of Biotechnology, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur 522510, India.
  • 2 Medicinal Chemistry and Pharmacology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500 007, India.
  • 3 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad 500 037, India.
  • 4 Medicinal Chemistry and Pharmacology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500 007, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad 500 037, India. Electronic address: ahmedkamal@iict.res.in.
PMID: 28400235 DOI: 10.1016/j.bmcl.2017.03.089
Abstract

Based on our previous results and literature precedence, a series of 2-anilinopyridinyl-benzothiazole Schiff Bases were rationally designed by performing molecular modeling experiments on some selected molecules. The binding energies of the docked molecules were better than the E7010, and the Schiff base with trimethoxy group on benzothiazole moiety, 4y was the best. This was followed by the synthesis of a series of the designed molecules by a convenient synthetic route and evaluation of their Anticancer potential. Most of the compounds have shown significant growth inhibition against the tested cell lines and the compound 4y exhibited good antiproliferative activity with a GI50 value of 3.8µM specifically against the cell line DU145. In agreement with the docking results, 4y exerted cytotoxicity by the disruption of the microtubule dynamics by inhibiting tubulin polymerization via effective binding into colchicine domain, comparable to E7010. Detailed binding modes of 4y with colchicine binding site of tubulin were studied by molecular docking. Furthermore, 4y induced Apoptosis as evidenced by biological studies like mitochondrial membrane potential, Caspase-3, and Annexin V-FITC assays.

Keywords

Benzothiazole; Cell cycle; Cytotoxicity; E7010; Tubulin polymerization.

Figures