title: Design and synthesis of some novel 4-Chloro-N-(4-(1-(2-(2-cyanoacetyl)hydrazono)ethyl)phenyl) benzenesulfonamide derivatives as anticancer and radiosensitizing agents.
abstract: A novel series of sulfonamide derivatives 4-21 have been synthesized starting from the strategic starting material (E)-4-Chloro-N-(4-(1-(2-(2-cyanoacetyl)hydrazono)ethyl)phenyl) benzenesulfonamide 4. Two series of hydrazone 5-9, and pyridone 10-21 derivatives bearing a sulfonamide moiety were obtained. All the newly synthesized compounds were evaluated for their in vitro cytotoxic activity against human liver cancer cell line (HepG2). Compounds 4-6, 8, 9, 10-14 and 16-18 showed higher activity compared to doxorubicin as a positive control. The radiosensitizing ability of the most promising compounds 4, 10 and 12 was studied which showed an increase in the cell killing effect of γ-radiation after combination with these derivatives. The molecular design was performed to predict the binding mode of the most promising compounds 4, 10 and 12 with the active site of hCA IX, that showed appropriate fitting with the relevant amino acids in the binding pocket on the basis of standard bond lengths, angles, S score and E conformation data.
authors.affiliation: Department of Drug Radiation Research, National Center for Radiation Research and Technology, Nasr City, Cairo, Egypt; Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia. Electronic address: mmsghorab@yahoo.com.
authors.forename: Mostafa M
authors.initials: MM
authors.lastname: Ghorab
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Cairo University, Egypt.
authors.forename: Fatma A
authors.initials: FA
authors.lastname: Ragab
authors.affiliation: Department of Drug Radiation Research, National Center for Radiation Research and Technology, Nasr City, Cairo, Egypt.
authors.forename: Helmy I
authors.initials: HI
authors.lastname: Heiba
authors.affiliation: Department of Drug Radiation Research, National Center for Radiation Research and Technology, Nasr City, Cairo, Egypt.
authors.forename: Aiten M
authors.initials: AM
authors.lastname: Soliman
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005720:Gamma Rays; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D013449:Sulfonamides; D000096926:Benzenesulfonamides
keywords: Anticancer; Radiosensitizers; Sulfonamide