t. brucei

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).

DDD85646 is an inhibitor of T. brucei N-myristoyltransferase with a Ki of 1.44 nM, an IC50 of 2 nM and an EC50 of 2 nM. The IC50 of hNMT is 4 nM.

CRK12-IN-1 is a potent CRK12 inhibitor with insecticidal activity and exhibits inhibitory effects on Trypanosoma brucei (T.b. brucei) and Trypanosoma congolense (T. congolense) with EC50s of 1.3 and 18 nM, respectively, rapidly killing the pathogenic cells.

Acoziborole (SCYX-7158), a derivative of benzoxaborole, is a safe, effective and structurally novel antigen-worm agent for human African trypanosomiasis (HAT) studies. The MIC value of Acoziborole for T. b. brucei S427 was 0.6 µg/mL.

1. Lycobetaine (Ungeremine) is a potential biofungicide against Penicillium roqueforti and Aspergillus niger.2. Lycobetaine have strong antibacterial activity against Flavobacterium columnare . 3. Lycobetaine effectively targets mammalian as well as bacterial type I and type II topoisomerases.4. Lycobetaine shows strong acetylcholinesterase inhibitory activity(IC(50) value of 0.35 microM). 5. Lycobetaine has antiprotozoal activity, it shows good activity in in vitro assays against Trypanosoma brucei rhodesiense, T. cruzi.

Jaspamycin (7-CN-7-C-Ino) does not bind with purified human PKARIα but exhibits anti-parasite activity and is a potent activator of PKA, binding to the R site (PKAR) with an EC50 of 6.5 nM and a Kd of 8 nM in Trypanosoma brucei.

NPD1335, a potent inhibitor of Trypanosoma brucei phosphodiesterase B1 (TbrPDEB1), exhibits submicromolar activity against T. brucei parasites and an improved cytotoxicity profile. By elevating intracellular cAMP levels, NPD1335 disrupts the cell cycle, leading to cell death [1].

Tuberculosis inhibitor 1 is a potent, non-cytotoxic inhibitor of Trypanosoma brucei growth [EC50: 5 nM].

DNA crosslinker 6 (compound 1) is an anti-mitotic agent known for its strong binding affinity to AT-DNA and inhibition of AT-hook 1 binding to DNA (IC50=0.03 µM). Additionally, it exhibits anti-protozoal activity, effectively inhibiting T. brucei with an EC50 of 0.83 µM.

Proteasome-IN-6 (Compound J-80) inhibits the β5 catalytic subunit of the Trypanosoma brucei 20S proteasome, effectively blocking T. b. brucei, T. b. gambiense, and T. b. rhodesiense with EC50 values of 157 nM, 220 nM, and 156 nM, respectively. Additionally, Proteasome-IN-6 has demonstrated antitrypanosomal activity in a mouse model.

PFK-IN-1 (compound 1) is an inhibitor of 6-phosphofructo-1-kinase (PFK), demonstrating IC50 values of 0.41 and 0.23 μM against T. brucei and T. cruzi PFK, respectively, and an ED50 of 15.18 μg mL for T. brucei. The compound has a half-life of 9.7 minutes in rat liver microsomes and 408 minutes in mouse liver microsomes.

Antiparasitic agent-24 (Compound 14a) is an antiparasitic compound with EC50 values of 0.005 μM for L. maj, 0.069 μM for L. don, 0.82 μM for T. brucei, and 4.1 μM for T. cruzi.

NEU-1017 serves as a broad-spectrum antiparasitic compound, effectively inhibiting T. brucei, L. major, and P. falciparum with EC50 values of 210 nM, 240 nM, and 3 nM, respectively.

GSK2188764 is an inhibitor of T. brucei IPMK, partially inhibits rTbIPMK activity.

Megazol is a nitroimidazole based drug that cures some protozoan infections. A study of nitroimidazoles found the drug extremely effective against T. cruzi and T. brucei which cause Chagas disease and African sleeping sickness, respectively.

NEU-1045 is a T. brucei proliferation inhibitor, and is a promising lead with cross-pathogen activity. NEU-1045 inhibited T. brucei, T. cruzi, and L. major proliferation with good potency (T. brucei EC50 = 0.37 μM; T. cruzi EC50 = 2.8 μM; L. major EC50 =

NEU-1923 is a potent inhibitor of T. brucei proliferation (EC50= 0.37 μM).

NEU-730, a novel inhibitor of TbrPDEB1, shows modest inhibition of T. brucei proliferation.

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)

O-11 is an analog of the fully saturated, 14-carbon fatty acid myristic acid, in which the methylene group at position 11 is replaced with oxygen. It is highly effective and selective at killingTrypanosoma brucei, the protozoan parasite responsible for African sleeping sickness, exhibiting an LD50of less than 1 μM in a cell culture assay.1,2The toxic effects of O-11 appear to be caused by its ability to inhibit the incorporation of a single myristate into the GPI anchor of the variant surface glycoprotein (VSG), a protein critical for evading the host immune response.1O-11 exhibits essentially no anti-fungal activity when assayed usingC. neoformans, but does have a minor inhibitory effect on HIV-1 replication in T-lymphocytes.3 1.Doering, T.L., Raper, J., Buxbaum, L.U., et al.An analog of myristic acid with selective toxicity for African trypanosomesScience2521851-1854(1991) 2.Doering, T.L., Lu, T., Werbovetz, K.A., et al.Toxicity of myristic acid analogs toward African trypanosomesProceedings of the National Academy of Sciences of the United States of America919735-9739(1994) 3.Langner, C.A., Lodge, J.K., Travis, S.J., et al.4-Oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus IThe Journal of Biological Chemisty267(24)17159-17169(1992)

7-Methylguanosine 5'-diphosphate (7-Methyl-GDP) sodium, a cap analog, is utilized in the synthesis of mRNA cap analogues[1].

Ajugol (Leonuride) shows some trypanocidal potential against Trypanosoma brucei rhodesiense (IC50 values 29.3–73.0 ug ml).

Hygrolidin is a macrocyclic lactone originally isolated from S. hygroscopicus. It inhibits proliferation of a variety of cancer cell lines, including DLD-1 colon cancer, LNCaP prostate cancer, and K562 leukemia cells (IC50s = 2.9, 5.2, and 33 ng ml, respectively). Hygrolidin induces the expression and levels of p21 in DLD-1 cells, but not WI-38 fibroblasts, and leads to cell accumulation in the G1 and S phases without inducing apoptosis. It has antiparasitic activity against T. cruzi, L. donovani, and T. b. brucei but also induces cytotoxicity in HepG2 cells (IC50s = 1.1, 72.5, 77, and 24.5 nM, respectively).

1. Xanthatin has cytotoxic activity. 2. Xanthatin has antibacterial and antifungal activies against MRSA. 3. Xanthatin may have therapeutic potential against NSCLC. 4. Xanthatin can inhibit murine melanoma B16-F1 cell proliferation possibly associated wit