Search results for "Dual inhibitor"
showing 3 items of 3 documents
Dual inhibitors of histone deacetylases and other cancer-related targets: A pharmacological perspective.
2020
International audience; Epigenetic enzymes histone deacetylases (HDACs) are clinically validated anticancer drug targets which have been studied intensively in the past few decades. Although several drugs have been approved in this field, they are still limited to a subset of hematological malignancies (in particular T-cell lymphomas), with therapeutic potential not fully realized and the drug-resistance occurred after a certain period of use. To maximize the therapeutic potential of these classes of anticancer drugs, and to extend their application to solid tumors, numerous combination therapies containing an HDACi and an anticancer agent from other mechanisms are currently ongoing in clin…
Synthesis and inhibitory activity of dimethylamino-chalcone derivatives on the induction of nitric oxide synthase.
2002
A series of nine dimethylamino-chalcone derivatives (1,3-diaryl-propenones) was synthesized and screened as potential inhibitors of NO and PGE(2) production in the RAW 264.7 macrophage cell line. 4-Dimethylamino-2',5'-dimethoxychalcone (6) was found to be the most potent and dual inhibitor (IC(50s) in the submicromolar range) of NO and PGE(2) production. 2',6'-Dimethoxylation appeared to be an effective requirement for selective and potent inhibition of nitric oxide synthase induction as it was confirmed by Western blot analysis. Chalcone (6) at 25 mg kg(-1) by oral route, inhibited significantly the formation of oedema in the carrageenan-induced model of inflammation in mice.
Non-steroidal anti-inflammatory agents. Part 23. Synthesis and Pharmacological Activity of Enaminones which inhibit both bovine cyclooxygenase and 5-…
1998
The synthesis and stereochemical characteristics of pyrrolidino-, isoquinolino- and indolo-enaminones 2–11 are reported. The inhibition of cyclooxygenase was determined in a bovine thrombocyte intact cell assay and that of 5-lipoxygenase using intact bovine polymorphonuclear leucocytes. Except compound 2c′ which is a well-balanced dual inhibitor of both enzymes, all other enaminone derivatives are weak inhibitors of both cyclooxygenase and 5-lipoxygenase. Structure-activity relationships of the enaminones in relation to known anti-inflammatory drugs are discussed.