Reversible Carnitine Palmitoyltransferase Inhibitors with Broad Chemical Diversity as Potential Antidiabetic Agents
Journal of Medicinal Chemistry2001Vol. 44(15), pp. 2383–2386
Citations Over TimeTop 20% of 2001 papers
Fabio Giannessi, P. Chiodi, Mauro Marzi, Patrizia Minetti, Pompeo Pessotto, Francesco De Angelis, Emanuela Tassoni, Roberto Conti, Fabrizio Giorgi, Massimo Mabilia, Natalina Dell’Uomo, Sandra Muck, Maria Ornella Tinti, Paolo Carminati, Arduino Arduini
Abstract
A series of carnitine related compounds of general formula XCH(2)CHZRCH(2)Y were evaluated as CPT I inhibitors in intact rat liver (L-CPT I) and heart mitochondria (M-CPT I). Derivative 27 (ZR = -HNSO(2)R, R = C(12), X = trimethylammonium, Y = carboxylate, (R) form) showed the highest activity (IC(50) = 0.7 microM) along with a good selectivity (M-CPT I/L-CPTI IC(50) ratio = 4.86). Diabetic db/db mice treated orally with 27 showed a significant reduction of serum glucose levels.
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