ULTRASOUND-ASSISTED SYNTHESIS AND DOCKING STUDY OF NOVEL CHROMONE-THIADIAZOLE INTEGRATED PHOSPHONATE DERIVATIVES TARGETING TOPOISOMERASE II AS ANTICANCER AGENTS

Abstract

Objective: The present studies discuss the anticancer activity of different topoisomerase II inhibitors with docking study.
 Methods: The work reports the synthesis of novel diethyl (4-oxo-4H-chromen-3-yl)(5-substituted phenyl-1,3,4-thiadiazol-2-ylamino)methyl phosphonate derivatives 6(a-j). They were synthesized through one-pot three-component Kabachnik-Fields reaction by using ultrasonicator processor, at room temperature in presence of Zirconium oxychloride (ZrOCl2).
 Results: The structures of the synthesized compounds were confirmed by spectral analysis. The synthesized derivatives 6(a-j) were evaluated for their in vitro anticancer activity against human cancer cell lines such as DU 145 (Human Prostate Cancer) and MCF-7 (Breast cancer) and also on non-tumor cell lines such as MCF-10 (normal breast epithelial cell) by MTT assay. From the anticancer screening results data, compound 6e was found to be the most potent anticancer compound among the synthesized compounds against MCF-7 and DU 145 cancer cell lines with IC50 value of 2.97 µM and 3.11 µM, respectively. The compound 6h has shown cell cycle arrest at G2/M phase, along with the decrease of cells at G0/G1 phage. The compound 6h was able to induce apoptosis in DU 145 cell lines. The synthesized compounds 6(a-j) were further evaluated for their topoisomerase II inhibitory activity.
 Conclusion: The anticancer screening result and MTT assay, along with the docking study shows that the synthesised derivative are active anticancer agent against MCF-10, DU-145 and MCF-7 cell line.