- Design, synthesis and biological evaluation of novel thiazole-derivatives as mitochondrial targeting inhibitors of cancer cells
-
Mitochondria are pivotal energy production sources for cells to maintain necessary metabolism activities. Targeting dysfunctional mitochondrial features has been a hotspot for mitochondrial-related disease researches. Investigation with cancerous mitochondrial metabolism is a continuing concern within tumor therapy. Herein, we set out to assess the anti-cancer activities of a novel family of TPP-thiazole derivatives based on our earlier research on mitochondrial targeting agents. Specifically, we designed and synthesized a series of TPP-thiazole derivatives and revealed by the MTT assay that most synthesized compounds effectively inhibited three cancer cell lines (HeLa, PC3 and MCF-7). After structure modifications, we explored the SAR relationships and identified the most promising compound R13 (IC50 of 5.52 μM) for further investigation. In the meantime, we performed ATP production assay to assess the selected compounds inhibitory effect on HeLa cells energy production. The results displayed the test compounds significantly restrained ATP production of cancer cells. Overall, we have designed and synthesized a series of compounds which exhibited significant cytotoxicity against cancer cells and effectively inhibited mitochondrial energy production.
- Dang, Xin,Lei, Shuwen,Luo, Shuhua,Hu, Yixin,Wang, Juntao,Zhang, Dongdong,Lu, Dan,Jiang, Faqin,Fu, Lei
-
-
- CARBACEPHEM BETA-LACTAM ANTIBIOTICS
-
Carbacephem β-lactam antibiotics having structure (I) are disclosed, including stereoisomers, pharmaceutically acceptable salts, esters and prodrugs thereof, wherein Ar2, X, R1 and R2 are as defined herein. The compounds are useful for the treatment of bacterial infections, in particular those caused by methicillin-resistant Staphylococcus spp.
- -
-
Page/Page column 79-80
(2010/04/06)
-
- QUINOLONES USEFUL AS INDUCIBLE NITRIC OXIDE SYNTHASE INHIBITORS
-
The present invention relates to novel quinolones of Formula I that inhibit inducible NOS synthase together with methods of synthesizing and using the compounds including methods for inhibiting or modulating nitric oxide synthesis and/or lowering nitric oxide levels in a patient by administering the compounds for the treatment of disease.
- -
-
Page/Page column 55
(2008/12/06)
-
- Selective Bromination of 4,5-Dimethylthiazole with N-Bromosuccinimide
-
Radical bromination of 4,5-dimethylthiazole (1) was carried out using different stoichiometries of N-bromosuccinimide in the presence of 2,2'-azobisisobutyronitrile.Mono-, tri- and tetrabromo compounds 2, 5, and 6 were obtained in good yields with regioselectivity while the dibromo derivatives 3 and 4 were formed without any selectivity.Substitution at the thiazole ring occurred in the presence of silica gel or in the perfluoro ether FC-77 (C8F16O), affording the 2-bromothiazole 7.The order of reactivity observed was 5-Me > 4-Me > C-2.Structural assignment of compounds 2-7 was made by chemical correlations and NMR spectroscopy. - Keywords: Heterocycles; NBS bromination; Selective bromination; Polybrominated thiazole; Structure elucidation
- Hariri, Mouaffak Al,Galley, Olivier,Pautet, Felix,Fillion, Houda
-
p. 593 - 594
(2007/10/03)
-