Synthesis, computational studies and biological evaluation of novel Acenaphthoquinone-imidazole derivatives as dual inhibitors of HSP90 and Topo II in cancer therapy

In this study, titled compounds (4a-4j) were synthesized by employing one-pot multicomponent reaction. To evaluate the binding affinity of derivatives against topo II/Hsp90 performed insilico molecular simulations. Using web tools ADMET and drug-likeness properties were predicted. The conjugation in the compound was confirmed by 1H NMR, 13C NMR, UV, Mass, and IR spectral studies. All the compounds showed the highest binding score compared to standard doxorubicin. These synthesized compounds exhibited moderate toxicities. The anticancer activity of the synthesized compounds was studied against cancer cell lines A-549(lung), HeLa (cervical), Du - 145 (prostate), Hep-G2 (liver) and one normal cell line (NHDF) using MTT assay. Among all the compounds 4a, 4e, 4f and 4i exhibited highly potent activity against all against cell lines compared to doxorubicin standard anticancer drug. The results propose that these compounds can act as leads to design dual inhibitors for cancer treatment.