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

Bioorganic & Medicinal Chemistry Letters
Thokhir Basha ShaikAhmed Kamal


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.


Dec 28, 1999·Annual Review of Cell and Developmental Biology·I BudihardjoX Wang
Oct 26, 2000·Nature·M O Hengartner
May 6, 2004·Journal of the National Cancer Institute·Shi-Yong SunReuben Lotan
Jan 19, 2008·Molecular Cancer Therapeutics·Kelly HuberStewart Martin
Sep 13, 2008·EMBO Reports·Anthony CormierBenoît Gigant
Jan 8, 2009·Journal of Natural Products·David G I Kingston
Jan 14, 2009·Annals of Hematology·Jia-Kun ShenJie Jin
Apr 9, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Edward L Schwartz
Jun 18, 2010·European Journal of Medicinal Chemistry·Ahmed KamalShasi V Kalivendi
May 1, 2012·Bioorganic & Medicinal Chemistry·Ahmed KamalAnthony Addlagatta
Jul 21, 2012·Pharmaceutical Research·Yan LuDuane D Miller
Aug 13, 2014·Proceedings of the National Academy of Sciences of the United States of America·Andrea E ProtaMichel O Steinmetz
Dec 4, 2014·Bioorganic & Medicinal Chemistry·Ahmed KamalChandrakant Bagul
Jan 8, 2015·Bioorganic & Medicinal Chemistry·Arvind S NegiRituraj Konwar

Related Concepts

Dye Exclusion Assays, Antitumor
Schiff Bases
Structure-Activity Relationship
TUBE1 gene
Drug Modeling
Tertiary Protein Structure
Cell Line, Tumor
Cell Proliferation
Antimitotic Agents

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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis