الفهرس | Only 14 pages are availabe for public view |
Abstract A general survey about the cancer, anti-cancer drugs and their mechanism of action, as well as a survey about the methods of synthesis of indoline-2,3-dione. Finally, a small introduction about different approaches of computer aided drug design for that purpose. The docking studies on CDK2 and GSK-3β inspired me to synthesis a series of indoline-2,3-dione hydrazones 10a-l. Treatment of indoline-2,3-dione derivatives 7a-d with hydrazine gave 3-hydrazonoindolin-2-ones 8a-d which were reacted with the appropriate aldehydes 9a-c to yield 3-substituted-(methylenehydrazono)indolin-2-ones 10a-l. Compounds 10a-l showed a significant anticancer activity against human breast cell line MCF-7. Compounds 10c, f, i exhibited the highest activity almost the same of doxorubicin (IC50 = 6.10 µM) with IC50 = 7.75, 6.75, 6.25 µM, respectively. The present investigation involves the synthesis of the following new intermediates: 1- 3-((Furan-2-ylmethylene)hydrazono)indolin-2-one (10a) 2- 3-((Furan-2-ylmethylene)hydrazono)-5-methylindolin-2-one (10b) 3- 5-Chloro-3-((furan-2-ylmethylene)hydrazono)indolin-2-one (10c) 4- 5-Fluoro-3-((furan-2-ylmethylene)hydrazono)indolin-2-one (10d) 5- 3-((Thiophen-2-ylmethylene)hydrazono)indolin-2-one (10e) 6- 5-Methyl-3-((thiophen-2-ylmethylene)hydrazono)indolin-2-one (10f) 7- 5-Chloro-3-((thiophen-2-ylmethylene)hydrazono)indolin-2-one (10g). 8- 5-Fluoro-3-((thiophen-2-ylmethylene)hydrazono)indolin-2-one (10h) 9- 3-(((1H-Pyrrol-2-yl)methylene)hydrazono)indolin-2-one (10i) 10- 3-(((1H-Pyrrol-2-yl)methylene)hydrazono)-5-methylindolin-2-one (10j). 11- 3-(((1H-Pyrrol-2-yl)methylene)hydrazono)-5-chloroindolin-2-one (10k). 12- 3-(((1H-Pyrrol-2-yl)methylene)hydrazono)-5-fluoroindolin-2-one (10l). |