Mahaveer Singh*, Hemant R. Jadhav* and Amit Kumar Pages 866 - 874 ( 9 )
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 33.20µM and 21.22µM, respectively, which is comparable to standard (gefitinib, IC50 value: 16.56 µM). These compounds, in HCT-116 colon cancer line, showed IC50 values of 11.33µM and 45.89µM which was again comparable to gefitinib that showed IC50 value of 10.51µM. Also, in MIAPaCa-2 cell line, compound C-14 showed IC50 value of <1µM. 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.
Carcinoma, cytotoxocity, epidermal growth factor receptor inhibitors, gefitinib, ethyl piperazine, cancer line.
Birla Institute of Technology and Sciences Pilani, Pilani Campus, Vidya Vihar, Pilani-333031, Rajasthan, Birla Institute of Technology and Sciences Pilani, Pilani Campus, Vidya Vihar, Pilani-333031, Rajasthan, Cancer Pharmacology Division, Indian Institute of Integrative medicine, Canal Road, Jammu-180001