2. Academic Validation
  3. Design and synthesis of new pyranoquinolinone heteroannulated to triazolopyrimidine of potential apoptotic antiproliferative activity

Design and synthesis of new pyranoquinolinone heteroannulated to triazolopyrimidine of potential apoptotic antiproliferative activity

  • Bioorg Chem. 2020 Dec;105:104392. doi: 10.1016/j.bioorg.2020.104392.
Mohamed Ramadan 1,  Mohamed Abd El-Aziz 2,  Yassin A M M Elshaier 3,  Bahaa G M Youssif 4,  Alan B Brown 5,  Hazem M Fathy 6,  Ashraf A Aly 7
Affiliations

Affiliations

  • 1 Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, 71524 Assuit, Egypt. Electronic address: [email protected].
  • 2 Medicinal Department, Faculty of Pharmacy, Minia University, 61519 El Minia, Egypt.
  • 3 Organic and Medicinal Chemistry Department, Faculty of Pharmacy, University of Sadat City, 32958 Menoufia, Egypt.
  • 4 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. Electronic address: [email protected].
  • 5 Chemistry Department, Florida Institute of Technology, Melbourne, FL 32901, USA.
  • 6 Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, 71524 Assuit, Egypt.
  • 7 Chemistry Department, Faculty of Science, Minia University, 61519 El-Minia, Egypt. Electronic address: [email protected].
PMID: 33137557 DOI: 10.1016/j.bioorg.2020.104392
Abstract

Pyrano[3,2-c]quinoline derivatives have been synthesized and utilized to obtain various new hetero-annulated triazolopyrimidine, containing quinoline, pyran, 1,2,4-triazine and pyrimidine in good yields. Newly synthesized compounds have been characterized by spectral data and elemental analysis. Most of the synthesized compounds showed moderate to weak antiproliferative activity on most Cancer cell lines, especially leukemia and breast Cancer cell lines. The open chain formimidic acid ethyl ester is slightly more potent than hetero-annulated systems. The most active compounds were further investigated for Caspase activation, Bax activation and Bcl-2 down regulation compared to doxorubicin as a standard, and indeed exhibited mainly cell cycle arrest at the Pre-G1 and G2/M phases. The transcription effects of 5a and 5b on the p53 were assessed and compared with the reference doxorubicin. The results revealed an increase of 12-19 in p53 level compared to the test cells and that p53 protein level of 5a and 5b was significantly inductive (991, and 639 pg/mL, respectively) in relation to doxorubicin (1263 pg/mL).

Keywords

Antiproliferative; Apoptosis; Caspase; Formimidic acid; Pyrano[3,2-c]quinoline; Triazolopyrimidine.

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