52632-05-0Relevant articles and documents
Design, synthesis, and biological evaluation of novel EGFR inhibitors containing 5-chloro-3-hydroxymethyl-indole-2-carboxamide scaffold with apoptotic antiproliferative activity
Mohamed, Fatma A.M.,Gomaa, Hesham A.M.,Hendawy,Ali, Asmaa T.,Farghaly, Hatem S.,Gouda, Ahmed M.,Abdelazeem, Ahmed H.,Abdelrahman, Mostafa H.,Trembleau, Laurent,Youssif, Bahaa G.M.
supporting information, (2021/05/26)
New EGFR inhibitor series of fifteen 5-chloro-3-hydroxymethyl-indole-2-carboxamide derivatives has been designed, synthesized, and tested for antiproliferative activity against a panel of cancer cell lines. The results showed that p-substituted phenethyl derivatives 10, 11, 13, 15 and 17–19 showed superior antiproliferative activity compared to their m-substituted counterparts 12, 14, 16 and 20. Compounds 15, 16, 19 and 20 displayed promising EGFR inhibitory activity as well as an increase in caspase 3 levels. Compounds 15 and 19 increased caspase-8 and 9 levels, as well as inducing Bax and decreasing Bcl-2 protein levels. Compound 19 demonstrated cell cycle arrest at pre-G1 and G2/M phases. The results of the docking study into the active site of EGFR revealed strong fitting of the new compounds with higher binding affinities compared to erlotinib.
Design and synthesis of novel 2,3-dihydropyrazino[1,2-a]indole-1,4-dione derivatives as antiproliferative EGFR and BRAFV600E dual inhibitors
Abdelrahman, Mostafa H.,Abdu-Allah, Hajjaj H. M.,Abou-Ghadir, Ola F.,Al-Wahaibi, Lamya H.,Ali, Asmaa T.,Farghaly, Hatem S.,Gouda, Ahmed M.,Salem, Ola I. A.,Trembleau, Laurent,Youssif, Bahaa G. M.
, (2020/09/15)
Recent studies have shown additive and synergistic effects associated with the combination of kinase inhibitors. BRAFV600E and EGFR are attractive targets for many diseases treatments and have been studied extensively. In keeping with our interest in developing anticancer targeting EGFR and BRAFV600E, a novel series of 2,3-dihydropyrazino[1,2-a]indole-1,4-dione has been rationally designed, synthesized and evaluated for their antiproliferative activity against a panel of four human cancer cell lines. Compounds 20–23, 28–31, and 33 showed promising antiproliferative activities. These compounds were further tested for their inhibitory potencies against EGFR and BRAFV600E kinases with erlotinib as a reference drug. Compounds 23 and 33 exhibited equipotency to doxorubicin against the four cell lines and efficiently inhibited both EGFR (IC50 = 0.08 and 0.09 μM, respectively) and BRAFV600E (IC50 = 0.1 and 0.29 μM, respectively). In cell cycle study of MCF-7 cell line, compounds 23 and 33 induced apoptosis and exhibited cell cycle arrest in both Pre-G1 and G2/M phases. Molecular docking analyses revealed that the new compounds can fit snugly into the active sites of EGFR, and BRAFV600E kinases. Compound 23, 31 and 33 adopted similar binding orientations and interactions to those of erlotinib and vemurafenib.
Design, synthesis and pharmacophoric model building of new 3-alkoxymethyl/3-phenyl indole-2-carboxamides with potential antiproliferative activity
Abdelrahman, Mostafa H.,Aboraia, Ahmed S.,Youssif, Bahaa G. M.,Elsadek, Bakheet E. M.
, p. 64 - 82 (2017/06/19)
Novel 3-alkoxymethyl/3-phenyl indole-2-carboxamide derivatives were synthesized and evaluated for their anticancer activity. Most of the tested compounds showed moderate to excellent activity against the tested cell lines (MCF7 and HCT116). 3-Phenyl substitution on indole with p-piperidinyl phenethyl 24a and p-dimethylamino phenethyl 24c exhibited anticancer activity against MCF7 with IC50 of 0.13 and 0.14?μm, respectively. Further mechanistic study of the most active compounds through their action on cell cycle showed disturbance in cell cycle progression and cell cycle arrest. For future development of this series of compounds, pharmacophore study was conducted which indicated that the enhancement of the activity could be achieved through the addition of acceptor or donating groups to the already-present indole nucleus.
