trypanothione

Trypanothione, a bis-glutathionyl derivative present in trypanosomatids, offers protection against oxidative stress [1] [2] [3].

Antitrypanosomal agent 1 is a potent and selective trypanothione reductase (TR) inhibitor (IC50: 3.3 μM) that also inhibits glutathione reductase (IC50: 64.8 μM) and T. brucei (EC50: 1 μM).

Trypanothione synthetase-IN-5 (compound 9) is an inhibitor of trypanothione reductase (TR), showing an IC50 of 20.5 μM against Leishmania infantum TR. It also exhibits inhibitory activity against human glutathione reductase (hGR), with an IC50 of 62.4 μM.

Trypanothione synthetase-IN-4, a L. infantumTryS inhibitor, exhibits a strong anti-leishmanicidal effect (EC50: 0.6 μM, SI) dependent on the concentration of the polyamine substrate and can be used to study leishmaniasis.

Trypanothione Synthetase-IN-1 (Compound 1) serves as a competitive inhibitor of Leishmania infantum trypanothione synthetase (TryS), demonstrating an IC50 value of 14.8 μM in the presence of the polyamine S, triamine spermidine [1].

Trypanothione Synthetase-IN-2 (Compound 3) functions as a competitive inhibitor of Leishmania infantum trypanothione synthetase (TryS), demonstrating an inhibition constant (IC50) of 5.4 μM in the presence of the polyamine S, triamine spermidine [1].

Trypanothione Synthetase-IN-3, a mixed noncompetitive inhibitor of Trypanothione Synthetase (TryS) with an inhibition constant (Ki) of 0.8 μM, is useful in researching parasites like L. infantum [1].

Ebsulfur is a benzisothiazolone parasitic inhibitor targeting the trypanothione reductase (TryR) of Trypanosoma brucei, with an IC50 value ranging from 61 to 293 nM for this parasite. Ebsulfur is utilized in the study of African trypanosomiasis.

(E)-Ajoene is a disulfide that has been found inA. sativumand has diverse biological activities.1,2,3,4It is active against Gram-positive and Gram-negative bacteria (MICs = 10-250 and 150->500 μg/ml, respectively) and fungi (MICs = 15-50 μg/ml).1(E)-Ajoene inhibits proliferation of a variety of cancer cells, including MDA-MB-231 breast, HeLa cervical, and WHCO1 esophageal cancer cells (IC50s = 18.6, 61, and 39.2 μM, respectively).2It also inhibits human glutathione reductase andT. cruzitrypanothione reductase when used at a concentration of 200 μM.3(E)-Ajoene (25 mg/kg) is neuroprotective in a gerbil model of ischemia-reperfusion injury, reducing reactive astrocytosis and microgliosis in the hippocampal CA1 region.4 1.Yoshida, H., Iwata, N., Katsuzaki, H., et al.Antimicrobial activity of a compound isolated from an oil-macerated garlic extractBiosci. Biotechnol. Biochem.62(5)1014-1017(1998) 2.Kaschula, C.H., Hunter, R., Hassan, H.T., et al.Anti-proliferation activity of synthetic ajoene analogues on cancer cell-linesAnticancer Agents Med. Chem.11(3)260-266(2011) 3.Gallwitz, H., Bonse, S., Martinez-Cruz, A., et al.Ajoene is an inhibitor and subversive substrate of human glutathione reductase and Trypanosoma cruzi trypanothione reductase: Crystallographic, kinetic, and spectroscopic studiesJ. Med. Chem.42(3)364-372(1999) 4.Yoo, D.Y., Kim, W., Nam, S.M., et al.Neuroprotective effects of Z-ajoene, an organosulfur compound derived from oil-macerated garlic, in the gerbil hippocampal CA1 region after transient forebrain ischemiaFood Chem. Toxicol.721-7(2014)

2-Fluoro-4-iodo benzonitrile is a building block.1,2It has been used in the synthesis ofL. infantumtrypanothione reductase (Li-TryR) dimerization and oxidoreductase activity inhibitors.12-Fluoro-4-iodo benzonitrile has also been used in the synthesis of transient receptor potential ankyrin 1 (TRPA1) antagonists.2 1.Revuelto, A., Ruiz-Santaquiteria, M., de Lucio, H., et al.Pyrrolopyrimidine vs imidazole-phenyl-thiazole scaffolds in nonpeptidic dimerization inhibitors of Leishmania infantum trypanothione reductaseACS Infect. Dis.5(6)873-891(2019) 2.Vallin, K.S., Sterky, K.J., Nyman, E., et al.N-1-Alkyl-2-oxo-2-aryl amides as novel antagonists of the TRPA1 receptorBioorg. Med. Chem. Lett.22(17)5485-5492(2012)

Chinifur is a selective inhibitor and subversive substrate for Trypanosoma congolense trypanothione reductase

Antileishmanial agent-23 (compound G1/9), a potent and selective trypanothione reductase (TR) inhibitor, exhibits an IC50 of 2.24 ± 0.52 μM and effectively inhibits the growth of Leishmania, Trypanosoma cruzi, and Trypanosoma brucei [1].

Kukoamine A possesses anticancer, cytoprotective, antioxidant, and anti-inflammatory activities, it also has neuroprotective effects through inhibiting oxidative stress and apoptosis after whole-brain irradiation (WBI) in rats.