24 research outputs found
N-substituted benzamides inhibit NFκB activation and induce apoptosis by separate mechanisms
Benzamides have been in clinical use for many years in treatment against various disorders. A recent application is that as a sensitizer for radio- or chemotherapies. We have here analysed the mechanism of action of N-substituted benzamides using an in vitro system. We found that while procainamide was biologically inert in our system, the addition of a chloride in the 3′ position of the benzamide ring created a compound (declopramide) that induced rapid apoptosis. Furthermore, declopramide also inhibited NFκB activation by inhibition of IκBβ breakdown. An acetylated variant of declopramide, N-acetyl declopramide, showed no effect with regard to rapid apoptosis induction but was a potent inhibitor of NFκB activation. In fact, the addition of an acetyl group to procainamide in the 4′ position was sufficient to convert this biologically inactive substance to a potent inhibitor of NFκB activation. These findings suggest two potential mechanisms, induction of early apoptosis and inhibition of NFκB mediated salvage from apoptosis, for the biological effect of N-substituted benzamides as radio- and chemo-sensitizers. In addition it suggests that N-substituted benzamides are potential candidates for the development of anti-inflammatory compounds using NFκB as a drug target. © 1999 Cancer Research Campaig
ChemInform Abstract: 2-Arylindan-1,3-diones. Part 4. Synthesis of N1- and N2-Substituted-2-( pyridazin-3-yl)indan-1,3-diones and Crystal Structure of 2-(1- Methylpyridazin-3-io)indan-1,3-dionate.
ChemInform Abstract: 2-Arylindan-1,3-diones. Part 3. Synthesis of N-Substituted 2-(4H-1,2,4-Triazol-5-yl and 1H-Tetrazol-5-yl)indan-1,3-diones and Crystal Structure of 2-(4-Ethyl-1-methyl-4,5-dihydro-1H-tetrazol-5-ylidene)indan-1,3-dione
ChemInform Abstract: Indan-1,3-diones. Part 9. Synthesis and Antiinflammatory Activity of 2- Polyaza-arylindan-1,3-diones and Their N- or O-Substituted Derivatives.
EVALUATION ET EXPLORATION DES MECANISMES D'ACTION DE NOUVEAUX DERIVES AZOLYLBENZYLINDOLES ANTILEISHMANIENS ET ANTIFONGIQUES (DOCTORAT PARASITOLOGIE ET MYCOLOGIE MEDICALE )
NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF
Synthesis and Evaluation of Disubstituted N1- and N3-Imidazolidin-2-ones Acting as Potential Immunosuppressive Agents
International audienc
Synthesis and antileishmanial activity of new imidazolidin-2-one derivatives
International audienc
Synthesis andIn Vitro Evaluation of 3-(1-Azolylmethyl)-1H-indoles and 3-(1-Azolyl-1-phenylmethyl)-1H-indoles as Inhibitors of P450 arom
International audienc
In Vitro Activity of a New Antifungal Azolyl-substituted Indole Against Aspergillus fumigatus
Antileishmanial activities and mechanisms of action of indole-based azoles
International audienc