332019-04-2Relevant academic research and scientific papers
Isatin-Schiff's base and chalcone hybrids as chemically apoptotic inducers and EGFR inhibitors; design, synthesis, anti-proliferative activities and in silico evaluation
Fayed, Eman A.,Eldin, Rogy R. Ezz,Mehany, Ahmed,Bayoumi, Ashraf H.,Ammar, Yousry A.
, (2021)
Isatin derivatives have been found to possess anti-proliferative effects against different human cancer cell lines. A series of isatin-Schiff's base and chalcone were synthesized and screened for their anticancer activities against three human cell lines which are: MCF-7, HepG-2, and HCT-116. All the tested compounds exhibited moderate to high antitumor activity with IC50 ranging from 0.68–35.60 μM compared to Imatinib as a reference standard. Compounds 2b, 5, 8b, 12, 13a and 13b were the most active, with IC50 ranging from 0.68 to 5.85 μM for the three cell lines. The most active structures were selected for further investigations. Firstly, the IC50 values on normal human cells (WI-38) have been studied to ensure the safety of our hits, which showed that our new compounds have exhibited (IC50 >165.98 μM) as far as their cytotoxic effect is concerned. Moreover, up-regulation of BAX and Caspase-3 and down-regulation of Bcl-2 resulted in the induction of apoptosis from those active compounds. Further work has shown that the most potent derivative 8b, caused cell cycle arrest at the G2/M phase. Also, EGFR inhibitory activity for 8b showed IC50 0.014 μM versus wild EGFRWT and 12.66 nM versus the mutant type, Lapatinib, and Erlotinib were used as reference standards with IC50 values of 0.025, 0.0653 μM and 35.72, 59.56 nM versus both, respectively. Furthermore, the in-silico assessment showed that all-potent compounds were orally bioavailable without blood-brain barrier permeation. Finally, the molecular docking of 8b inside the active site of EGFR (1M17) showed a good binding through three hydrogen bonds and one arene-cation interaction.
New chalcones bearing isatin scaffold: synthesis, molecular modeling and biological evaluation as anticancer agents
Ammar, Yousry A.,Fayed, Eman A.,Bayoumi, Ashraf H.,Ezz, Rogy R.,Alsaid, Mansour S.,Soliman, Aiten M.,Ghorab, Mostafa M.
, p. 6765 - 6786 (2017/09/06)
Abstract: Derivatives of isatin have been reported to possess cytotoxic effects against different human carcinoma cell lines. A series of new isatin-linked chalcones was synthesized starting from isatin. Most of the newly synthesized compounds were screened for their in vitro anticancer activity against human breast (MCF-7), liver (HepG-2), and colon (HCT-116) cancer cell lines. All the tested compounds exhibited antitumor activity, with IC50 ranging from 2.88 to 62.88?μM in comparison to the reference drug used in this study, Imatinib. Compounds 2–5 were the most active, with IC50 ranging from 2.88 to 18.12?μM for the three cell lines, while compound 7b also showed moderate activity against HepG-2, MCF-7 and HCT-116 with IC50 13.95, 31.66 and 11.78?μM, respectively. Furthermore, compound 7d showed high activity against HepG-2 cells with IC50 12.84?μM. Compound 4 was shown to be the most potent against both HepG-2 and HCT-116 cell lines, while compound 2 is the most potent against MCF-7. The compounds were also screened for their cytotoxic activity against normal breast cell line MCF-12A, and were found to possess mild cytotoxicity. A docking study was performed for the most active compounds in this study, 2–5, inside the active site of CDK2. All the docked compounds have shown favorable binding interactions and energy scores. Compound 4 has proved to be the best in binding interactions and energy score. These findings may explain the cytotoxic activity of the target compounds. Graphical Abstract: A novel series of isatin-linked chalcones was synthesized. The target compounds were evaluated for their cytotoxic activity towards human breast (MCF-7), liver (HepG-2), colon (HCT-116) cancer cell lines and (MCF-12A) normal breast cell line.
