succinate dehydrogenase-in-1

Succinate dehydrogenase-IN-1 (Compound 34) acts as an inhibitor of succinate dehydrogenase (SDH), exhibiting an IC50 value of 0.94 μM and a KD of 22.4 μM. This compound also demonstrates antifungal activity, with EC50 values against Rhizoctonia solani, Sclerotinia sclerotiorum, Monilinia fructicola, and Botrytis cinerea measured at 0.04 μM, 1.13 μM, 1.61 μM, and 1.21 μM, respectively.

Boscalid is a broad-spectrum carboxamide fungicide that inhibits fungal respiration by binding to the ubiquinone site of mitochondrial complex II/succinate dehydrogenase.1It suppresses mycelial growth ofS. minorby 87 to 100% and ofS. sclerotiorumby 77 to 100% when used at a concentration of 1 μg/ml.2In field studies, boscalid applied at 5.6 μg/cm2provides 55.5 and 30.4% disease control for lettuce drop caused byS. minorandS. sclerotiorum, respectively. It decreases cell viability of mouse primary cortical neurons following long-term exposure but is not cytotoxic (LC50= >100 μM for acute and continuous exposure). Formulations containing boscalid have been used in agriculture to prevent fungal growth on crops. 1.Wang, Y., Duan, Y., Wang, J., et al.A new point mutation in the iron-sulfur subunit of succinate dehydrogenase confers resistance to boscalid in Sclerotinia sclerotiorumMol. Plant Pathol.16(7)653-661(2015) 2.Matheron, M.E., and Porchas, M.Activity of boscalid, fenhexamid, fluazinam, fludioxonil, and vinclozolin on growth of Sclerotinia minor and S. sclerotiorum and development of lettuce dropPlant Dis.88(6)665-668(2004)

N-Desbutyl dronedarone is an active metabolite of the antiarrhythmic agent dronedarone .1,2,3It is formed from dronedarone by cytochrome P450s (CYPs) and monoamine oxidase (MAO) in human hepatocyte preparations.4N-Desbutyl dronedarone inhibits the binding of 3,3',5-triiodo-L-thyronine to the thyroid hormone receptors TRα1and TRβ1(IC50s = 59 and 280 μM for the chicken and human receptors, respectively).1It inhibits CYP2J2-mediated formation of 14,15-EET from arachidonic acid and soluble epoxide hydrolase-mediated formation of 14,15-DHET from 14,15-EET (IC50s = 1.59 and 2.73 μM, respectively, in cell-free assays).2N-Desbutyl dronedarone decreases intracellular ATP levels in H9c2 rat cardiomyocytes (IC50= 1.07 μM) and inhibits mitochondrial complex I, also known as NADH dehydrogenase, and mitochondrial complex II, also known as succinate dehydrogenase, activities in isolated rat heart mitochondria (IC50s = 11.94 and 24.54 μM, respectively).3 1.Van Beeren, H.C., Jong, W.M.C., Kaptein, E., et al.Dronerarone acts as a selective inhibitor of 3,5,3'-triiodothyronine binding to thyroid hormone receptor-α1: in vitro and in vivo evidenceEndocrinology144(2)552-558(2003) 2.Karkhanis, A., Tram, N.D.T., and Chan, E.C.Y.Effects of dronedarone, amiodarone and their active metabolites on sequential metabolism of arachidonic acid to epoxyeicosatrienoic and dihydroxyeicosatrienoic acidsBiochem. Pharmacol.146188-198(2017) 3.Karkhanis, A., Leow, J.W.H., Hagen, T., et al.Dronedarone-induced cardiac mitochondrial dysfunction and its mitigation by epoxyeicosatrienoic acidsToxicol. Sci.163(1)79-91(2018) 4.Klieber, S., Arabeyre-Fabre, C., Moliner, P., et al.Identification of metabolic pathways and enzyme systems involved in the in vitro human hepatic metabolism of dronedarone, a potent new oral antiarrhythmic drugPharmacol. Res. Perspec.2(3)e00044(2014)

Sitamaquine is an antileishmanial agent.1It is active againstL. donovani,L. infantum,L. mexicana,L. braziliensis, andL. tropica(EC50s = 9.5-19.8 μM). It inhibits mitochondrial complex II, also known as succinate dehydrogenase (SDH), in a cell-free assay when used at concentrations ranging from 10 to 200 μM.2Sitamaquine (100 μM) increases intracellular levels of reactive oxygen species (ROS) and decreases intracellular ATP levels, as well as induces phosphatidylserine externalization, chromatin fragmentation, and depolarization of the mitochondrial membrane potential, markers of apoptosis, inL. donovanipromastigotes. 1.López-Martín, C., Pérez-Victoria, J.M., Carvalho, L., et al.Sitamaquine sensitivity in Leishmania species is not mediated by drug accumulation in acidocalcisomesAntimicrob. Agents Chemother.52(11)4030-4036(2008) 2.Carvalho, L.J.M., Luque-Ortega, J.R., López-Martín, C., et al.The 8-aminoquinoline analogue sitamaquine causes oxidative stress in Leishmania donovani promastigotes by targeting succinate dehydrogenaseAntimicrob. Agents Chemother.55(9)4204-4210(2011)

SDH-IN-1 (compound 4i) is an SDH (succinate dehydrogenase) inhibitor (IC50 = 4.53 μM) with antifungal activity against S. sclerotiorum (EC50 = 0.14 mg/L) and can be used for fungicidal purposes.

Penflufen, a broad-spectrum succinate dehydrogenase inhibitor (SDHI), serves effectively as a fungicide. It demonstrates broad bioactivity against a variety of fungal diseases such as potato black scurf, wheat sharp eyespot, rice sheath blight, and root rot in peanuts, among others [1].

SDH-IN-4 (compound B6) is a selective succinate dehydrogenase (SDH) inhibitor with an IC50 of 0.28 µg/mL, demonstrating potent antifungal effects, including an EC50 of 0.23 µg/mL against R. solani [1].

SDH-IN-7 (compound G28) is a potent inhibitor of succinate dehydrogenase (SDH) with an IC50 value of 26 nM against porcine SDH and possesses fungicidal properties [1].

SDH-IN-8 (compound G40) is a potent succinate dehydrogenase (SDH) inhibitor with an IC50 of 27 nM against porcine SDH and exhibits fungicidal properties [1].

SDH-IN-5 (compound 7d), a potent inhibitor of succinate dehydrogenase (SDH) with an IC50 of 3.293 μM, additionally demonstrates antifungal efficacy, exhibiting an EC50 of 0.046 μg/mL against R. solani. Moreover, SDH-IN-5 significantly hampers R. solani growth in rice leaves, showcasing outstanding protective and curative effects [1].

SDH-IN-3 is a succinate dehydrogenase (SDH) inhibitor with potent antifungal activity, demonstrating an inhibition concentration (IC50) of 7.2 μg/mL and an effective concentration (EC50) of 1.9 μg/mL against Nigrospora oryzae, making it valuable for anti-infection research [1].

SDH-IN-6 (compound 6i), a potent inhibitor of succinate dehydrogenase (SDH), exhibits antifungal efficacy against Valsa mali, demonstrated by an EC50 value of 1.77 mg/L [1].

SDH-IN-9 (compound Ip) is a potent Succinate Dehydrogenase inhibitor with fungicidal properties, effectively targeting Fusarium graminearum Schw at an EC50 of 0.93 μg/mL [1].

SDH-IN-10 is a potent succinate dehydrogenase inhibitor (SDHI) that exhibits antifungal activity [1].

SDH-IN-11 (compound A7), a succinate dehydrogenase (SDH) inhibitor, effectively curtails nematode feeding, reproduction, and egg hatching. It induces oxidative stress and intestinal damage in nematodes. Additionally, SDH-IN-11 impedes the enzymatic activity of SDH within these organisms [1].

SDH-IN-12 (compound 9b), a succinate dehydrogenase inhibitor, shows activity against S. sclerotiorum and C. arachidicola, with respective EC50 values of 0.97 and 2.07 μM. The compound demonstrates no significant herbicidal effects on monocotyledonous and dicotyledonous plants [1].