T3574

Sematilide hydrochloride (CK-1752) is a class III antiarrhythmic. It is a selectively delayed rectifier K+ current (IKr) channel blocker. It inhibits rapidly activating Ik in guinea pig atrial myocytes, resulting in the prolongation of refractoriness and action potential duration.

FR900098 is a derivative of fosmidomycin that has antimalarial activity (IC50s = 170, 170, and 90 nM for HB3, A2, and Dd2 P. falciparum strains, respectively). FR900098 inhibits DOXP reductoisomerase, a key enzyme in the non-mevalonate pathway of isoprenoid biosynthesis, in vitro in a dose-dependent manner. FR900098 (>10 mg/kg, i.p.) eradicated P. vinckei parasites within four days in mice.

Gliovirin is a fungal metabolite that has been found inT. harzianumand has fungicidal, antimicrobial and anti-inflammatory activities.1It is active against the plant pathogenic fungusP. ultimum(MIC = 60 ng/ml) and the parasiteT. brucei brucei(IC50= 90 ng/ml), but has no effect on the plant pathogenic fungiR. solani,P. omnivorum,T. basicola,R. arrhizus, andV. dahliaeor the bacteriaB. thuringiensis,P. fluorescens, andX. malvacearumwhen used at concentrations up to 1,000 ng/ml.2,3Gliovirin decreases phorbol 12-myristate 13-acetate (TPA)- and ionomycin-induced increased expression of COX-2 (IC50= 1 μM) and protein levels of IL-2 in Jurkat cells (IC50= 5.2 μM).1 1.Rether, J., Serwe, A., Anke, T., et al.Inhibition of inducible tumor necrosis factor-α expression by the fungal epipolythiodiketopiperazine gliovirinBiol. Chem.388(6)627-637(2007) 2.Howell, C.R., and Stipanovic, R.D.Gliovirin, a new antibiotic from Gliocladium virens, and its role in the biological control of Pythium ultimumCan. J. Microbiol.29(3)321-324(1983) 3.Iwatsuki, M., Otoguro, K., Ishiyama, A., et al.In vitro antitrypanosomal activity of 12 low-molecular-weight antibiotics and observations of structure/activity relationshipsJ. Antibiot. (Tokyo)63(10)619-622(2010)

Ivermectin B1a aglycone is a degradation product generated by acid hydrolysis of the disaccharide structure of ivermectin. It inhibits the growth and development of nematode larvae without causing paralytic effects.

Ivermectin B1a monosaccharide is produced by selective hydrolysis of the terminal saccharide unit of ivermectin. It can inhibit nematode larval development, but does not cause paralytic activity. This compound has been used as a probe to detect some types of ivermectin resistance.

Milbemycin A3 is a macrocyclic lactone compound produced by fermentation of Streptomyces hygroscopicus, characterized by a spiroketal structure. It enhances the activity of Glutamate-gated chloride channel and GABA-gated chloride channels, thereby disrupting neurotransmission in parasites and exhibiting acaricidal and nematocidal activities.

Quinacrine analog 34 is a potent autophagy inhibitor (EC₅₀ = 0.5 μM, LD₅₀ = 27 μM) that upregulates the protein levels of the autophagy marker LC3-II and induces lysosomal deacidification.

Thymohydroquinone (Thymoquinol) is a monoterpenoid phenolic compound found in thyme, oregano, and other plants in the labiaceae family. Thymohydroquinone inhibits cancer cell growth, reduces oxidative stress and modulates inflammatory responses, scoured 2, 2-diphenyl-1-PicrylHydrazyl radicals in a cell-free assay (IC50 = 2.4 μg/ml), In the oxygen radical absorption capacity (ORAC) test at concentrations of 1.6 to 6.4 μg/ml, Its Trolox value was 2.6. Thymus hydroquinone inhibited the growth of A2780, OVCAR-8 and CIS-A2780 ovarian cancer cells (IC50 were 3.1, 8.9 and 9.8 μM, respectively) and human ovarian immortalized epithelial cells (IC50 = 14 μM). It also inhibited Plasmodium falciparum in vitro (IC50 = 15.9 μM).