1187736-41-9Relevant academic research and scientific papers
Discovery of new quinolines as potent colchicine binding site inhibitors: design, synthesis, docking studies, and anti-proliferative evaluation
Hagras, Mohamed,El Deeb, Moshira A.,Elzahabi, Heba S. A.,Elkaeed, Eslam B.,Mehany, Ahmed B. M.,Eissa, Ibrahim H.
, p. 640 - 658 (2021)
Discovering of new anticancer agents with potential activity against tubulin polymerisation is still a promising approach. Colchicine binding site inhibitors are the most relevant anti-tubulin polymerisation agents. Thus, new quinoline derivatives have been designed and synthesised to possess the same essential pharmacophoric features of colchicine binding site inhibitors. The synthesised compounds were tested in?vitro against a panel of three human cancer cell lines (HepG-2, HCT-116, and MCF-7) using colchicine as a positive control. Comparing to colchicine (IC50 = 7.40, 9.32, and 10.41 μM against HepG-2, HCT-116, and MCF-7, respectively), compounds 20, 21, 22, 23, 24, 25, 26, and 28 exhibited superior cytotoxic activities with IC50 values ranging from 1.78 to 9.19 μM. In order to sightsee the proposed mechanism of anti-proliferative activity, the most active members were further evaluated in?vitro for their inhibitory activities against tubulin polymerisation. Compounds 21 and 32 exhibited the highest tubulin polymerisation inhibitory effect with IC50 values of 9.11 and 10.5 nM, respectively. Such members showed activities higher than that of colchicine (IC50 = 10.6 nM) and CA-4 (IC50 = 13.2 nM). The impact of the most promising compound 25 on cell cycle distribution was assessed. The results revealed that compound 25 can arrest the cell cycle at G2/M phase. Annexin V and PI double staining assay was carried out to explore the apoptotic effect of the synthesised compounds. Compound 25 induced apoptotic effect on HepG-2 thirteen times more than the control cells. To examine the binding pattern of the target compounds against the tubulin heterodimers active site, molecular docking studies were carried out.
Synthesis, structure-activity relationship and molecular docking studies of novel quinoline-chalcone hybrids as potential anticancer agents and tubulin inhibitors
Mirzaei, Salimeh,Hadizadeh, Farzin,Eisvand, Farhad,Mosaffa, Fatemeh,Ghodsi, Razieh
, (2020)
A new series of quinoline-chalcone hybrids was synthesized. The structures of these compounds were characterized by spectroscopic methods including 1H and 13CNMR and mass spectroscopy. The cytotoxic activity of compounds was evaluated against four human cancer cell lines including A2780 (human ovarian carcinoma) and A2780/RCIS (Cisplatin resistant human ovarian carcinoma), MCF-7 (human breast cancer cells), MCF-7/MX (Mitoxantrone resistant human breast cancer cells) and normal Huvec cells. The structure-activity relationship of synthesized compounds is discussed. Among quinolines 5e, 5g and 5j possessing benzoyl group showed significant cytotoxic activity against both resistant cancer cells and their parents. Compounds 5g and 5j, demonstrated the most antiproliferative activity with IC50 values ranging from 2.32 to 22.4 μM. They were also identified as tubulin inhibitors and induced cell cycle arrest at G2/M phase and apoptosis. Compound 5j induced more arrest at G2/M phase in four cancer cell lines compared to compound 5g. Finally, molecular dynamics simulation and molecular docking studies of compound 5j into the colchicine-binding site of tubulin demonstrated the possible interaction of this compound in the active site of tubulin.
Synthesis and characterization of pyrido[1,2-a]quinoline palladacycles
Hamad Elgazwy, Abdel-Sattar S.
experimental part, p. 1285 - 1297 (2009/12/04)
Palladacycles of pyrido[1,2-a]quinoline complexes were synthesized via a one pot reaction of quinolines with XyNC (Xy = 2,6-Me 2C 6H3) in the presence of Pd(dba)2 (4:1). These palladacycles were also obtained via reaction of quinolines with Pd(dba) 2 in the presence of PPh 3 (1:2) in acetone to give the intermediate complexes of dinuclear palladaphosphaquinoline complexes. Dinuclear complexes were converted into palladacycles via reaction with XyNC in CH 2Cl2. The crystal structure of the dinuclear palladium complex was determined by X-ray diffraction studies.
