Iten M Fawzy1, Khairia M Youssef1, Deena S Lasheen2, Nasser Sm Ismail1, Khaled Am Abouzid2. 1. Pharmaceutical Chemistry Department, Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University in Egypt, Cairo 12311, Egypt. 2. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
Abstract
AIM: Imatinib possesses various mechanisms for combating cancer, making the development of imatinib analogs an attractive target for cancer research. METHOD: Two series of analogs were designed and synthesized, maintaining the essential pharmacophoric features in imatinib structure. The synthesized compounds were subjected to cell-based antiproliferative assays against nonsmall lung (A549) and colon cancer cell lines. In addition, flow cytometry cell cycle and caspase-3 colorimetric assays were performed. RESULTS: Most compounds showed potent anticancer activity against both cell lines with IC50 = 0.14-5.07 μM. Three compounds demonstrated ability to reinforce cell cycle arrest at G1 stage in a manner similar to imatinib. In addition, they induced apoptosis via activation of caspase-3.
AIM: Imatinib possesses various mechanisms for combating cancer, making the development of imatinib analogs an attractive target for cancer research. METHOD: Two series of analogs were designed and synthesized, maintaining the essential pharmacophoric features in imatinib structure. The synthesized compounds were subjected to cell-based antiproliferative assays against nonsmall lung (A549) and colon cancer cell lines. In addition, flow cytometry cell cycle and caspase-3 colorimetric assays were performed. RESULTS: Most compounds showed potent anticancer activity against both cell lines with IC50 = 0.14-5.07 μM. Three compounds demonstrated ability to reinforce cell cycle arrest at G1 stage in a manner similar to imatinib. In addition, they induced apoptosis via activation of caspase-3.
Entities:
Keywords:
3D QSAR pharmacophore; caspase-3 induction; cytotoxicity; imatinib; protein kinase
Authors: Ibrahim F Nassar; Mohammed T Abdel Aal; Wael A El-Sayed; Mahmoud A E Shahin; Elsayed G E Elsakka; Mahmoud Mohamed Mokhtar; Maghawry Hegazy; Mohamed Hagras; Asmaa A Mandour; Nasser S M Ismail Journal: RSC Adv Date: 2022-05-17 Impact factor: 4.036
Authors: Asmaa A Mandour; Ibrahim F Nassar; Mohammed T Abdel Aal; Mahmoud A E Shahin; Wael A El-Sayed; Maghawry Hegazy; Amr Mohamed Yehia; Ahmed Ismail; Mohamed Hagras; Eslam B Elkaeed; Hanan M Refaat; Nasser S M Ismail Journal: J Enzyme Inhib Med Chem Date: 2022-12 Impact factor: 5.756