| Autor: |
Abd Elhameid MK; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University., Ryad N; Pharmaceutical Organic Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology., Al-Shorbagy MY; Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University.; School of pharmacy, Newgiza University., Mohammed MR; Department of Radiation Biology, National Center for Radiation Research and Technology., Ismail MM; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University.; Pharmaceutical Organic Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology., El Meligie S; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University. |
| Abstrakt: |
A new series of pyridine and pyrimidine derivatives is designed and synthesized as potential antitumor molecules. The tested compounds show promising in vitro cytotoxic activity against HL-60 cell line as eight compounds: 4, 6, 11, 13, 14, 15, 18 and 21 exhibit potent cytotoxic activity in sub-micromolar concentration higher than the combretastatin A4 (CA-4). Compound 21 shows a cytotoxic activity 5-fold more potent than CA-4 on HL-60 cells. DNA-Flow cytometry cell cycle analysis and annexin-V assay on HL-60 cells show that compounds 4, 18 and 21 exhibit potent cell growth inhibition, cell cycle arrest at G 2 /M phase and pro-apoptotic inducing activities. The percentage inhibition assay of β-tubulin polymerization on HL-60 cells shows that the antitumor activity of the tested compounds appears to correlate well with its ability to inhibit β-tubulin polymerization. In addition, enzyme-linked immunosorbene assay (ELlSA) measurement for compound 21 shows apoptotic inducing activities through significant up regulation of p53, Bax/Bcl-2 ratio and caspase-3 proteins parallel to down regulation of the level of survivin proteins. |
