Novel coumarin-6-sulfonamides as apoptotic anti-proliferative agents: synthesis, in vitro biological evaluation, and QSAR studies
Sabt, Ahmed; Abdelhafez, Omaima M.; El-Haggar, Radwan S.; Hassan M. F. Madkour; Eldehna, Wagdy M.; El-Khrisy, Ezz El Din A.M.; Abdel-Rahman, Mohamed A.; Rashed, Laila A.;
Abstract
Herein, we report the synthesis of different novel sets of coumarin-6-sulfonamide derivatives bearing different functionalities (4a, b, 8a–d, 11a–d, 13a, b, and 15a–c), and in vitro evaluation of their growth inhibitory activity towards the proliferation of three cancer cell lines; HepG2 (hepatocellular carcinoma), MCF-7 (breast cancer), and Caco-2 (colon cancer). HepG2 cells were the most sensitive cells to the influence of the target coumarins. Compounds 13a and 15a emerged as the most active members against HepG2 cells (IC50 = 3.48 ± 0.28 and 5.03 ± 0.39 µM, respectively). Compounds 13a and 15a were able to induce apoptosis in HepG2 cells, as assured by the upregulation of the Bax and downregulation of the Bcl-2, besides boosting caspase-3 levels. Besides, compound 13a induced a significant increase in the percentage of cells at Pre-G1 by 6.4-folds, with concurrent significant arrest in the G2-M phase by 5.4-folds compared to control. Also, 13a displayed significant increase in the percentage of annexin V-FITC positive apoptotic cells from 1.75–13.76%. Moreover, QSAR models were established to explore the structural requirements controlling the anti-proliferative activities.
Other data
Title | Novel coumarin-6-sulfonamides as apoptotic anti-proliferative agents: synthesis, in vitro biological evaluation, and QSAR studies | Authors | Sabt, Ahmed; Abdelhafez, Omaima M.; El-Haggar, Radwan S.; Hassan M. F. Madkour ; Eldehna, Wagdy M.; El-Khrisy, Ezz El Din A.M.; Abdel-Rahman, Mohamed A.; Rashed, Laila A. | Keywords | 2D-QSAR;Anticancer;Apoptosis;Coumarin-6-sulfonamides;Synthesis | Issue Date | 1-Jan-2018 | Journal | Journal of Enzyme Inhibition and Medicinal Chemistry | Volume | 33 | Issue | 1 | Start page | 1095 | End page | 1107 | ISSN | 14756366 | DOI | 10.1080/14756366.2018.1477137 | PubMed ID | 29944015 | Scopus ID | 2-s2.0-85049238576 |
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