Synthesis and cytotoxic activities of some pyrazoline derivatives bearing phenyl pyridazine core as new apoptosis inducers
- Eur J Med Chem. 2016 Apr 13:112:48-59. doi: 10.1016/j.ejmech.2016.01.048.
- 1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, El-kasr Elaini Street, Cairo 11562, Egypt. Electronic address: [email protected].
- 2. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, El-kasr Elaini Street, Cairo 11562, Egypt.
- 3. Biotechnology Sector, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, Egypt.
The cyclization of Chalcones 3a-3u with 3-hydrazinyl-6-phenylpyridazine 7 under basic condition led to the formation of new pyrazoline derivatives 8a-8u. All final compounds were characterized by spectral and elemental analyses. They were screened for their antiproliferative activities against A549 (lung), HepG-2 (liver), CaCo-2 (intestinal) and MCF-7 (breast) Cancer cell lines. Some of the synthesized compounds exhibited promising antiproliferative activities especially compound 8k with IC50 values of 8.33, 1.67 and 10 μM against HepG-2, MCF-7 and CaCo-2 Cancer cell lines, respectively. Moreover, their antiproliferative activity was due to Apoptosis rather than necrosis induction except compound 8h which exhibited equal apoptotic and necrotic properties. Compound 8k showed 5 fold increase in Caspase-3 activity indicating that the Apoptosis proceeds via Caspase-3 activation.