Synthesis and antitumor evaluation of novel cyclic arylsulfonylureas: ADME-T and pharmacophore prediction.
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-(1H,3H,5H)-triones (6a-l), and 3-(4-substituted)phenyl-1-(4-substituted)phenylsulfonylquinazoline-2,4(1H,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 microM). 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.
Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
Ibrahim M
IM
El-Deeb
Said M
SM
Bayoumi
Magda A
MA
El-Sherbeny
Alaa A-M
AA
Abdel-Aziz
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013453:Sulfonylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*
D000970:Antineoplastic Agents; D013453:Sulfonylurea Compounds