title: Synthesis and cytotoxic activities of some pyrazoline derivatives bearing phenyl pyridazine core as new apoptosis inducers.
abstract: 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.
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, El-kasr Elaini Street, Cairo 11562, Egypt. Electronic address: rihamfgeorge@yahoo.com.
authors.forename: Riham F
authors.initials: RF
authors.lastname: George
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, El-kasr Elaini Street, Cairo 11562, Egypt.
authors.forename: Marwa A
authors.initials: MA
authors.lastname: Fouad
authors.affiliation: Biotechnology Sector, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, Egypt.
authors.forename: Iman E O
authors.initials: IEO
authors.lastname: Gomaa
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D011724:Pyridazines; D053148:Caspase 3
keywords: Apoptosis; Caspase-3; Chalcones; MTT assay; Pyrazolylpyridazines