Design, Synthesis and In Vitro Evaluation of Piperazine Incorporated Novel Anticancer Agents

Background: Novel 4-(3-(4-ethylpiperazin-1-yl) propoxy)-N-phenylbenzamide derivatives (C-1 to C-10) and (4-(3-(4-ethylpiperazin-1-yl) propoxy) phenyl)(4-(2-methoxyphenyl)piperazin-1-yl) ethanone derivatives (C-11 to C-16) were designed and synthesized by pharmacophore approach. Methods: All compounds were evaluated for their in-vitro cytotoxicity against a panel of three cancer cell lines (A-549 human lung carcinoma, HCT-116 colon cancer and pancreatic cancer MIAPaCa-2). Results: The results indicated that in A-549 human lung carcinoma cell line, compounds C-4 and C-5 showed IC50 values of 33.20 mu M and 21.22 mu M, respectively, which is comparable to standard (gefitinib, IC50 value: 16.56 mu M). These compounds, in HCT-116 colon cancer line, showed IC50 values of 11.33 mu M and 45.89 mu M which was again comparable to gefitinib that showed IC50 value of 10.51 mu M. Also, in MIAPaCa-2 cell line, compound C-14 showed IC50 value of <1 mu M. To give mechanistic basis, in silico docking studies were done and it shows good in silico - in vitro correlation. Conclusion: These results provide an encouraging lead that could be used for the development of new potent anticancer agents.