2. Academic Validation
  3. 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

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

  • Eur J Med Chem. 2014 Aug 18:83:155-66. doi: 10.1016/j.ejmech.2014.06.027.
Mohamed Fares 1,  Sahar Mahmoud Abou-Seri 2,  Hatem A Abdel-Aziz 3,  Safinaz E-S Abbas 4,  Mohieldin Magdy Youssef 5,  Radwa Ahmed Eladwy 6
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, College of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt.
  • 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, P.O. Box 11562, Egypt. Electronic address: saharshaarawy_69@yahoo.com.
  • 3 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Applied Organic Chemistry, National Research Center, Dokki, Giza, P.O. Box 12622, Egypt. Electronic address: hatem_741@yahoo.com.
  • 4 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, P.O. Box 11562, Egypt.
  • 5 Department of Pharmacology and Toxicology, College of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt; Department of Biology, School of Science and Engineering (SSE), American University in Cairo, New Cairo, P.O. Box 11835, Egypt.
  • 6 Department of Pharmacology and Toxicology, College of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt.
PMID: 24956552 DOI: 10.1016/j.ejmech.2014.06.027
Abstract

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.

Keywords

Antitumor activity; Apoptosis; Cell cycle arrest; Pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine; Pyrido[2,3-d]pyrimidine.

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