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.
El-Deeb
Ibrahim M
IM
Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
Bayoumi
Said M
SM
El-Sherbeny
Magda A
MA
Abdel-Aziz
Alaa A-M
AA
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