| Affiliation: | 1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, 44519 Zagazig, Egypt Department of Chemistry and Physics, Augusta University, 30912 Augusta, GA, USA;2. Department of Chemistry and Physics, Augusta University, 30912 Augusta, GA, USA;3. Department of Pesticide Chemistry, National Research Centre, Dokki, 12622 Giza, Egypt;4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, 11562 Cairo, Egypt;5. Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo (AUC), 11835 Cairo, Egypt;6. Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, 89081 Ulm, Germany;7. Drug Bioassay-Cell Culture Laboratory, Pharmacognosy Department, National Research Centre, Dokki, 12622 Giza, Egypt;8. Department of Chemistry, Birla Institute of Technology and Science, Pilani, India;9. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, 21589 Jeddah, Saudi Arabia;10. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, 44519 Zagazig, Egypt |
| Abstract: | Three sets of isatin-based Schiff bases were synthesized utilizing the molecular hybridization approach. Some of the synthesized Schiff bases show significant to moderate antiproliferative properties against MCF7 (breast), HCT116 (colon), and PaCa2 (pancreatic) cancer cell lines with potency compared to reference drugs 5-fluorouracil (5-FU) and Sunitinib. Among all, compound 17 f (3-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino)-1-((1-(2-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methylindolin-2-one) exhibits promising antiproliferative properties against the MCF7 cancer cell line with 2.1-fold more potency than Sunitinib. However, among all the synthesized compounds, three (5-methylisatin derivatives) were the most effective against HCT116 in comparison to 5-FU. Compound 17 f exhibited the highest anti-angiogenic effect on the vasculature as it significantly reduced BV from 43 mm to 2 mm in comparison to 5.7 mm for Sunitinib and flow cytometry supports the arrest of the cell cycle at G1/S phases. In addition, compound 17 f also showed high VEGFR-2 inhibition properties against breast cancer cell lines. Robust 2D-QSAR studies supported the biological data. |
