Format

Send to

Choose Destination
Bioorg Med Chem. 2017 Apr 1;25(7):2210-2217. doi: 10.1016/j.bmc.2017.02.037. Epub 2017 Feb 21.

Synthesis of bulky-tailed sulfonamides incorporating pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-1(5H)-yl) moieties and evaluation of their carbonic anhydrases I, II, IV and IX inhibitory effects.

Author information

1
School of Chemistry, University of Wollongong, Wollongong 2522, New South Wales, Australia; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. Electronic address: ph.fares@yahoo.com.
2
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt.
3
Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019 Sesto, Fiorentino, Firenze, Italy; Università degli Studi di Firenze, Neurofarba Department., Sezione di Scienze Farmaceutiche, Laboratory of Molecular Modeling Cheminformatics & QSAR, via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
4
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt.
5
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
6
Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
7
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafr El-Sheikh 33516, Egypt.
8
Department of Applied Organic Chemistry, National Research Center, Dokki, Giza 12622, Egypt.
9
Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019 Sesto, Fiorentino, Firenze, Italy. Electronic address: claudiu.supuran@unifi.it.

Abstract

Using celecoxib as lead, two novel series of sulfonamides incorporating the pyridotriazolopyrimidine scaffold have been synthesized and evaluated in vitro as inhibitors against four relevant human (h) carbonic anhydrases (CAs, EC 4.2.1.1), the cytosolic and ubiquitous hCA I and II as well as the transmembrane hCA IV and hCA IX. Most of the reported sulfonamides acted as efficient, low micromolar inhibitors of hCAI, II and IV, whereas they displayed higher efficacy in inhibiting the tumor-associated isoform hCA IX. Many derivates herein reported showed better hCA IX versus hCA II selectivity ratios compared to celecoxib or acetazolamide. Considering isoform IX is a validated target for the diagnosis and treatment of hypoxic tumors, discovery of selective CA IX inhibitors represents a promising step to unveil more effective anticancer therapies.

KEYWORDS:

Carbonic anhydrase; Celecoxib; Pyridotriazolopyrimidine; Sulfonamide; Tumor-associated isoforms

PMID:
28256371
DOI:
10.1016/j.bmc.2017.02.037
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center