TITLE:
Molecular Modeling and Synthesis of New Heterocyclic Compounds Containing Pyrazole as Anticancer Drugs
AUTHORS:
Fiby N. Takla, Abdelbasset A. Farahat, Magda A.-A. El-Sayed, Magda N. A. Nasr
KEYWORDS:
Tubulin, CA-4, Anticancer, Pyrazole, Molecular Modeling
JOURNAL NAME:
International Journal of Organic Chemistry,
Vol.7 No.4,
December
15,
2017
ABSTRACT: Several modifications in CA-4 were reported in
literature for the development of various tubulin inhibitors. In our study,
twenty-two newly synthesized heterocyclic derivatives of Combretastatin A-4
(CA-4) have been tested for their cytotoxic effect on four different types of
cells with malignant behavior using CA-4 as a positive control. Compounds 5b, 15 and 16 showed the foremost potent antiproliferative activities
as compared to CA-4 with IC50 starting from 6.9 to 13.7 μM. Molecular docking
was performed with the crystal structure of tubulin employing a potent tubulin
inhibitor CA-4 as a parent molecule. Molecular study advised that 5b, 15, 16 and 17 are promising tubulin inhibitors.