Dapson in Heterocyclic Chemistry, Part V: Synthesis, Molecular Docking and Anticancer Activity of Some Novel Sulfonylbiscompounds Carrying Biologically Active Dihydropyridine, Dihydroisoquinoline, 1,3-Dithiolan, 1,3-Dithian, Acrylamide, Pyrazole, Pyrazolopyrimidine and Benzochromenemoieties

被引:22
作者
Ghorab, Mostafa Mohammed [1 ]
Al-Said, Mansour Sulaiman [1 ]
Nissan, Yassin Mohammed [2 ]
机构
[1] King Saud Univ, Coll Pharm, MAPPRC, Riyadh 11451, Saudi Arabia
[2] Cairo Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo 11562, Egypt
关键词
sulfone; pyridine; pyrazolopyrimidine; benzochromene; anticancer activity; FARNESYL-PROTEIN TRANSFERASE; ANTITUMOR ACTIVITIES; SULFONE BISCOMPOUNDS; IN-VIVO; AGENTS; CELLS; FARNESYLTRANSFERASE; CYTOTOXICITY; DERIVATIVES; METHYLTRANSFERASE;
D O I
10.1248/cpb.c12-00292
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
N,N'-(4,4'-Sulfonylbis(4,1-phenylene))bis(2-cyanoacetamid) 2 was utilized as a key intermediate for the synthesis of novel dihydropyridines 3, 4, 8, dihydroisoquinolines 5-7, dithiolan 10, dithian 11, acrylamide 12, benzochromenes 17 and 18 and chromenopyridones 19 and 20. Compound 2 was the starting material in the synthesis of the acrylamide derivative 14, the pyrazole derivative 15 and the pyrazolopyrimidine derivative 16. All the synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Compound 19 showed the best cytotoxic activity with IC50 value 19.36 mu M. In addition, molecular docking study of the synthesized compounds on the active sites of farnesyltransferase and arginine methyltransferase was performed in order to give a suggestion about the mechanism of action of their cytotoxic activity.
引用
收藏
页码:1019 / 1028
页数:10
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