Synthesis, characterization and investigation of antiproliferative activity of eight thiazole-based nitrogen mustard against
human cancer cells lines (MV4-11, A549, HCT116 and MCF-7) and normal mouse fibroblast (BALB/3T3) are presented. Their
structures were determined using NMR, FAB MS, HRMS and elemental analyses. Among the derivatives, 3a, 3b, 3e and 3h were found
to exhibit high activity against human leukemia MV4-11 cells with IC50 values of 0.634-3.61 µg/ml. The cytotoxic activity of compound
3a against BALB/3T3 cells is up to 40 times lower than against cancer cell lines. Our data indicated also that compound 3e had very
strong activity against MCF-7 and HCT116 with IC50 equal to 2.32 µg/ml and 2.81 µg/ml, respectively. Their activity was similar to the
activity of cis-platin, which is clinically used as anticancer drug in the treatment of human solid tumours. We also perform quantum
chemical calculation of interaction and binding energies in complexes of model systems and 3e with DNA bases. Interaction of real drug
3e with guanine is much stronger than with the remaining nucleobases, and the strongest among all investigated complexes. Computer
simulations were performed with ATP-binding domain and DNA-binding site of hTopoII. Compounds 3a-h were recognized as potential
inhibitors of hTopoII.
Keywords: Antiproliferative activity, DFT calculations, interaction energy, nitrogen mustard, nucleobases, thiazole.
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