title: Development of certain new 2-substituted-quinazolin-4-yl-aminobenzenesulfonamide as potential antitumor agents.
abstract: Carbonic anhydrases (CA I, II, IX and XII) are known to be highly expressed in various human malignancies. CA IX is overexpressed in colorectal cancer specifically in hereditary nonpolyposis colorectal cancer. Inhibition of CA activity by small molecular CA inhibitor like sulphonamides, sulphonamide derivative (SU.D2) or HIF1a inhibitor Chetomin leads to inhibition of tumorigenesis. Eighteen new quinazolin-4-sulfonamide derivatives were prepared and characterized by means of IR, NMR and mass spectra. Certain selected derivatives were tested for their ability to inhibit four isoforms of the metalloemzyme CA, namely, CA I, CA II, CA IX and CA XII. Compound 3c was found to be highly effective in inhibiting the cancer cell proliferation. 3c decreased cell viability of human HT-29 cells in dose and time dependent manner and with IC50 of 5.45 μM. Moreover, it was tested on metastatic colon cancer cell SW-620 where it was found to be equally effective on human SW-620 cells. This novel compound inhibited the CA IX and CA XII protein expression in HT-29 cells without affecting CA I and CA II expression. These findings indicate that 3c inhibits cellular proliferation in two human colon cancer cells by specifically targeting the CA IX and CA XII expression.
authors.affiliation: DAIS, Alkharj 11942, P.O. Box 217, Saudi Arabia. Electronic address: alafeefy@hotmail.com.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Alafeefy
authors.affiliation: Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, King Saud University College of Medicine, Riyadh 11451, Saudi Arabia. Electronic address: arehan@ksu.edu.sa.
authors.forename: Rehan
authors.initials: R
authors.lastname: Ahmad
authors.affiliation: Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, King Saud University College of Medicine, Riyadh 11451, Saudi Arabia.
authors.forename: Maha
authors.initials: M
authors.lastname: Abdulla
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt.
authors.forename: Wagdy M
authors.initials: WM
authors.lastname: Eldehna
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Alkharj, 11942, Saudi Arabia.
authors.forename: Abdul-Malek S
authors.initials: AM
authors.lastname: Al-Tamimi
authors.affiliation: Department of Applied Organic Chemistry, National Research Center, Dokki, Giza, P.O. Box 12622, Egypt; Pharmaceutical Research Department, Center of Excellence for Advanced Sciences, National Research Centre, P.O. Box 12622, Cairo, Egypt. Electronic address: hatem_741@yahoo.com.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Abdel-Aziz
authors.affiliation: Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, King Saud University College of Medicine, Riyadh 11451, Saudi Arabia.
authors.forename: Omar
authors.initials: O
authors.lastname: Al-Obaid
authors.affiliation: Università degli Studi di Firenze, NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carta
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Alkharj, 11942, Saudi Arabia; Chemistry Department, Faculty of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Abdulla A
authors.initials: AA
authors.lastname: Al-Kahtani
authors.affiliation: Università degli Studi di Firenze, NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D019073:HT29 Cells; D006801:Humans; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D011799:Quinazolines; D013449:Sulfonamides; D002256:Carbonic Anhydrases
keywords: Antitumor; Carbonic anhydrase; Quinazoline; Sulfonamides; Sulfonylthioureas