2. Academic Validation
  3. Synthesis and anticancer activity of new dihydropyrimidinone derivatives

Synthesis and anticancer activity of new dihydropyrimidinone derivatives

  • Eur J Med Chem. 2018 Aug 5:156:304-315. doi: 10.1016/j.ejmech.2018.07.004.
Amany S Mostafa 1,  Khalid B Selim 2
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
  • 2 Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. Electronic address: khbselim@mans.edu.eg.
PMID: 30015070 DOI: 10.1016/j.ejmech.2018.07.004
Abstract

A series of dihydropyrimidinone derivatives bearing various N-heterocyclic moieties was designed and synthesized. Twelve new compounds were screened for their cytotoxic activity using 60 Cancer cell lines according to NCI (USA) protocol. Compound 19 showed a significant activity against NCI-H460, SK-MEL-5, and HL-60 (TB) cell lines with growth inhibition 88%, 86% and 85%, respectively, and was found to be more safe on normal cells when compared to doxorubicin. Enzyme inhibition assay was performed for compound 19 against mTOR (IC50 = 0.64 μM) and VEGFR-2 (IC50 = 1.97 μM) to show high potency in comparison to rapamycin (IC50 = 0.43 μM) and sorafenib (IC50 = 0.3 μM) as references, respectively. Cell cycle analysis of A549 cells treated with 19 showed cell cycle arrest at G2/M phase and pro-apoptotic activity as indicated by annexin V-FITC staining.

Keywords

Anticancer; Apoptosis; Cell cycle analysis; Dihydropyrimidinone; VEGFR-2; mTOR.

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