1620563-97-4Relevant academic research and scientific papers
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
Fares, Mohamed,Eladwy, Radwa A.,Nocentini, Alessio,El Hadi, Soha R. Abd,Ghabbour, Hazem A.,Abdel-Megeed, Ashraf,Eldehna, Wagdy M.,Abdel-Aziz, Hatem A.,Supuran, Claudiu T.
, p. 2210 - 2217 (2017)
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.
An improved synthesis of pyrido[2,3-: D] pyrimidin-4(1 H)-ones and their antimicrobial activity
Fares, Mohamed,Abd El Hadi, Soha R.,Eladwy, Radwa A.,Shoun, Aly A.,Abdel-Aziz, Marwa M.,Eldehna, Wagdy M.,Abdel-Aziz, Hatem A.,Keller, Paul A.
, p. 3389 - 3395 (2018/05/23)
The screening of a small library of diverse chemical structures resulted in the identification of 2-thioxodihydropyrido[2,3-d]pyrimidine 10a as having broad spectrum antibacterial activity (MIC 0.49-3.9 μg mL-1), and reasonable antifungal activity (MIC 31.25 μg mL-1). An expeditious synthesis of 10a was optimized by varying solvents, catalysts and the use of microwave irradiation with the best conditions using DMF as a solvent, I2 (10 mol%) and a 30 minutes reaction time compared to 15 h for classic conventional heating. The pharmacokinetic properties and calculation of drug likeness of 10a suggested good traditional drug-like properties and led to the synthesis of a small library with seven compounds 10a and 10d-i showing broad antimicrobial activity (MIC = 0.49-7.81 μg mL-1) and selectivity indices of more than 5.6 against the normal colon cell line (CCD-33Co). The antifungal activity of compounds 10d-i was moderate to strong with MIC values of 1.95-15.63 μg mL-1.
Synthesis and antitumor activity of pyrido [2,3-d]pyrimidine and pyrido[2,3-d] [1,2,4]triazolo[4,3-a]pyrimidine derivatives that induce apoptosis through G1 cell-cycle arrest
Fares, Mohamed,Abou-Seri, Sahar Mahmoud,Abdel-Aziz, Hatem A.,Abbas, Safinaz E.-S.,Youssef, Mohieldin Magdy,Eladwy, Radwa Ahmed
, p. 155 - 166 (2014/07/08)
New series of 2-(2-arylidenehydrazinyl)pyrido[2,3-d]pyrimidines 5a-e and pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidines 6-15 were synthesized and evaluated for their cytotoxic activity against two cancer cell lines, namely PC-3 prostate cancer and A-549 lung cancer. Some of the tested compounds displayed high growth inhibitory activity against PC-3 cells. Whereas, compounds 5b and 15f showed relatively potent antitumor activity against PC-3 and A-549 cell lines. In particular, 4-(3-acetyl-5-oxo-6-phenyl-8-(thiophen-2-yl)pyrido[2, 3-d][1,2,4]triazolo[4,3-a]pyrimidin-1(5H)-yl)benzenesulfonamide 15f exhibited superior antitumor activity against both cell lines at submicromolar level (IC50 = 0.36, 0.41 μM, respectively). Moreover, the potential mechanisms of the cytotoxic activity of the promising compound 15f on the more sensitive cell line PC-3 were studied. The data indicated that 15f was able to cause cell cycle arrest at least partly through enhancing the expression level of the cell cycle inhibitor p21 and induced cancer cell apoptosis via caspase-3 dependent pathway.
