title: Novel Thiourea Derivatives Bearing Sulfonamide Moiety as Anticancer Agents Through COX-2 Inhibition.
abstract: BACKGROUND
  Thiourea derivatives bearing sulfonamide moiety are well known for their anticancer activity.
  
  
  OBJECTIVE
  The anticancer activity of the target compounds was studied, via inhibition of COX-2 enzyme.
  
  
  METHODS
  A series of novel thioureas 5a-n, 8, quinazoline 6, benzo[g]quinazoline 7 and benzo[1,3] dioxole 10, bearing a sulfonamide moiety was synthesized from the starting compound N-(2,6-dimethoxypyrimidin-4-yl)-4- isothiocyanatobenzenesulfonamide 2. The target compounds were screened against HepG2, MCF-7, Caco-2, HCT-116, PC-3 cancer cell lines and VERO-B normal cell line.
  
  
  RESULTS
  Out of all the tested compounds, compound 5c showed a broad selective cytotoxicity against HepG2, MCF-7, Caco-2 and PC-3 cancer cells. Moreover, a sensitization assay was performed on Caco-2 cells, and compound 5c proved to act as a chemosensitizer for cisplatin on colon cancer (Caco-2) cells. The target compounds were further screened in vitro for their anti COX1/COX2 activity and investigated in vivo as antiinflammatory agents against carrageenan-induced rat paw oedema model.
  
  
  CONCLUSIONS
  Compound 5g showed the most selective inhibitory activity against COX-2. While, compounds 5a, 6, 5m, 5n, 5g and 5i revealed significant anti-inflammatory effect as presented in carrageenan-induced oedema assay. Molecular docking of the tested compounds disclosed important binding modes which may be responsible for their anticancer activity via inhibition of the COX-2 enzyme.
authors.affiliation: Department of Pharmacognosy, College of Pharmacy, King-Saud University, P.O. Box 2457. Saudi Arabia.
authors.forename: Mostafa M
authors.initials: MM
authors.lastname: Ghorab
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Al-Azhar University, Assuit. Egypt.
authors.forename: Mohamed S A
authors.initials: MSA
authors.lastname: El-Gaby
authors.affiliation: Department of Pharmacognosy, College of Pharmacy, King-Saud University, P.O. Box 2457. Saudi Arabia.
authors.forename: Mansour S
authors.initials: MS
authors.lastname: Alsaid
authors.affiliation: Department Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assuit. Egypt.
authors.forename: Yaseen A M M
authors.initials: YAMM
authors.lastname: Elshaier
authors.affiliation: Department of Drug Radiation Research, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo. Egypt.
authors.forename: Aiten M
authors.initials: AM
authors.lastname: Soliman
authors.affiliation: Department of Chemistry, Faculty of Science, Mansura University, Mansura. Egypt.
authors.forename: Fardous F
authors.initials: FF
authors.lastname: El-Senduny
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Mansura University, Mansura. Egypt.
authors.forename: Farid A
authors.initials: FA
authors.lastname: Badria
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh. Saudi Arabia.
authors.forename: Abdelrahman Y A
authors.initials: AYA
authors.lastname: Sherif
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D013890:Thiourea
keywords: COX-2; Thiourea; cytotoxicity; docking; pyrimidine; sulfonamide