title: Synthesis and antitumor evaluation of novel diarylsulfonylurea derivatives: molecular modeling applications.
abstract: Some new ethyl 2-[3-(4-unsubstituted or 4-substituted phenylsufonyl)ureido]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylates 3a-c, 2-[3-(phenylsulfonyl)ureido]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carbohydrazides 4a-f, 3-phenylsulfonyl-6,7,8,9-tetrahydro-5H-cyclohepta[1',2':4,5]thieno[2,3-d]pyrimidine-2,4(1H,3H)dione 5 and 3-(phenylsulfonyl)-1-[3-(alkylaminocarbonyl or substituted piperazinylcarbonyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-2-yl]ureas 6a-d have been synthesized and tested for their antitumor activity. Among these compounds, 4a, 4c and 4d exhibited a broad spectrum antitumor activity with full panel (MG-MID) median growth inhibition (GI(50)) of 3.5, 4.9 and 4.0muM respectively. In addition, compounds 4c, 4d, 6c and 6d proved to be of moderate selectivity toward colon cancer cell lines with ratios of 3.1, 1.2, 3.6 and 3.0 respectively. Molecular modeling and pharmacophore prediction methods are used to study the antitumor activity of the most active compounds compared with the least active species by means of the molecular mechanic method.
authors: Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt. magda_m20@yahoo.com
authors: Magda A
authors: MA
authors: El-Sherbeny
authors: Alaa A-M
authors: AA
authors: Abdel-Aziz
authors: Musa A
authors: MA
authors: Ahmed
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D055672:Static Electricity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014508:Urea / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014508:Urea