title: 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.
abstract: 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 IC(50) value 19.36 µM. 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.
authors.affiliation: Medicinal, Aromatic and Poisonous Plants Research Center (MAPPRC), College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. mmsghorab@yahoo.com
authors.forename: Mostafa Mohammed
authors.initials: MM
authors.lastname: Ghorab
authors.forename: Mansour Sulaiman
authors.initials: MS
authors.lastname: Al-Said
authors.forename: Yassin Mohammed
authors.initials: YM
authors.lastname: Nissan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D020134:Catalytic Domain; D003622:Dapsone / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D051231:Farnesyltranstransferase / Q000737:chemistry / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular
chemical_list: D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D003622:Dapsone; D051231:Farnesyltranstransferase