Synthesis and antitumor evaluation of novel cyclic arylsulfonylureas: ADME-T and pharmacophore prediction

• Published in: European journal of medicinal chemistry 2010-06, Vol.45 (6), p.2516-2530
• Main Authors: El-Deeb, Ibrahim M., Bayoumi, Said M., El-Sherbeny, Magda A., Abdel-Aziz, Alaa A.-M.
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Biological and medical sciences; Cancer; Cell Line, Tumor; Cell Proliferation - drug effects; Diarylsulfonylurea; Drug Screening Assays, Antitumor - methods; General aspects; Humans; Hydrophobic and Hydrophilic Interactions; Imidazolidine; Medical sciences; Models, Molecular; Molecular Conformation; Molecular modeling; Pharmacology. Drug treatments; Pharmacophore; Pyrimidine; Quinazoline; Structure-Activity Relationship; Sulfonylurea Compounds - chemical synthesis; Sulfonylurea Compounds - chemistry; Sulfonylurea Compounds - pharmacology; Sulfonylurea Compounds - toxicity
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2010.02.038

Novel derivatives of 5-(substituted)benzylidene-3-(4-substituted)phenylsulfonylimidazolidine-2,4-diones ( 3a– r), 1-(4-substituted)phenylsulfonyl-3-(4-substituted)phenylpyrimidine-2,4,6-(1 H,3 H,5 H)-triones ( 6a– l), and 3-(4-substituted)phenyl-1-(4-substituted)phenylsulfonylquinazoline-2,4(1 H,3H)- diones ( 8a– l) have been synthesized and tested for their antitumor activity against 60 tumor cell lines taken from 9 different organs. The tested compounds have showed good inhibitory effect at the ovarian cancer (IGROV1) cell line. A significant inhibition for (RXF393) renal cancer cells was observed with series 3 compounds, while in the other two series 6 and 8, there was a significant inhibition of ovarian cancer cells (OVCAR-8) and melanoma cells (SK-MEL-2). Interestingly; beside the strong inhibition of compound 3q to IGROV1 and RXF393 cells, a great inhibition (199.62%) for (M14) Melanoma cells was observed at the tested concentration (10 μM). ADME-T and pharmacophore prediction methodology were used to study the antitumor activity of the most active compounds and to identify the structural features required for antitumor activity. [Display omitted]