title: Design, synthesis and in vitro antiproliferative activity of novel isatin-quinazoline hybrids.
abstract: Using a molecular hybridization approach, a new series of isatin-quinazoline hybrids 15a-o was designed and synthesized via two different synthetic routes. The target compounds 15a-o were prepared by the reaction of quinazoline hydrazines 12a-e with indoline-2,3-diones 13a-c or by treating 4-chloroquinazoline derivatives 11a-e with isatin hydrazones 14a-c. The in vitro anticancer activity of the newly synthesized hybrids was evaluated against the liver HepG2, breast MCF-7 and colon HT-29 cancer cell lines. A distinctive selective growth inhibitory effect was observed towards the HepG2 cancer cell line. Compounds 15b, 15g and 15l displayed the highest potency, with IC50 values ranging from 1.0 ± 0.2 to 2.4 ± 0.4 μM, and they were able to induce apoptosis in HepG2 cells, as evidenced by enhanced expression of the pro-apoptotic protein Bax and reduced expression of the anti-apoptotic protein Bcl-2, in addition to increased caspase-3 levels.
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, Egypt.
authors: Mohamed
authors: M
authors: Fares
authors: Wagdy M
authors: WM
authors: Eldehna
authors: Sahar M
authors: SM
authors: Abou-Seri
authors: Hatem A
authors: HA
authors: Abdel-Aziz
authors: Mohamed H
authors: MH
authors: Aly
authors: Mai F
authors: MF
authors: Tolba
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007510:Isatin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D061986:MCF-7 Cells; D015394:Molecular Structure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; C000595707:BCL2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D051028:bcl-2-Associated X Protein; D007510:Isatin; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Antiproliferative activity; Isatins; Molecular hybridization; Quinazolines