l. donovani

Amphotericin B (NSC-527017) is a polyene antifungal agent with broad-spectrum activity against many fungal species. Amphotericin B irreversibly binds to ergosterol and disrupts the integrity of cell membranes, resulting in antifungal activity.

2-Benzoxazolinone (2-Hydroxybenzoxazole) is found in cereals and cereal products. 2-Benzoxazolinone is found in rye seedlings.

GSK3494245 is a Leishmania donovani inhibitor that suppresses trypsin-like activity catalyzed by the β5 subunit of L. donovani proteasome, applicable for visceral leishmaniasis (VL) studies.

CHEMBL1276927 (N-(3-(1H-benzo[d]imidazol-2-yl)phenyl)-3-methylbenzamide) shows antibacterial and antiparasitic activities against Chlamydia pneumoniae and Leishmania donovani.

GSK3186899 is an inhibitor of Cdc2-related kinase 12 with an EC50 of 1.4 μM for L. donovani.

Compound 17k, also known as Antileishmanial agent-30, effectively inhibits Leishmania with an IC50 of 0.2 μM for L. donovani. It exhibits a CC50 of >100 μM and an SI of >500, indicating significant selectivity and potency.

Dihydrocyclosporin A (Dihydrocyclosporin-A) is closely related co-metabolite of cyclosporin A. Dihydrocyclosporin A significantly inhibits promastigotes and intracellular amastigotes.

1-Palmitoyl-2-hydroxy-sn-glycero-3-PE is a naturally occurring lysophospholipid and endogenous metabolite used in biochemical experiments and drug synthesis research.

Diacetylcercosporin, a perylenequinone produced by Cercospora and Septoria, exhibits diverse biological activities including inhibition of P. falciparum strains sensitive and resistant to chloroquine and L. donovani parasites (IC50 = 3.1 μM) in vitro. It shows cytotoxicity against SK-MEL, KB, BT549, and SK-OV-3 human cancer cell lines (IC50s = 4.8-8.7 μM) and acts as a phytotoxin, inhibiting the growth of lettuce and bentgrass at a concentration of 1.62 mM.

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)

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).

LXE408 is an orally active, kinetoplastid-selective proteasome inhibitor, exhibiting non-competitive inhibitory effects. It demonstrates an IC50 of 0.04 μM for L. donovani proteasome and an EC50 of 0.04 μM for L. donovani. Moreover, LXE408 shows limited ability to traverse the blood-brain barrier. Hence, LXE408 holds promise for advancing research in the field of visceral leishmaniasis (VL).

LXE408 fumarate is an orally active, non-competitive and kinetoplastid-selective proteasome inhibitor. LXE408 fumarate has an IC50 of 0.04 μM for L. donovani proteasome and an EC50 of 0.04 μM for L. donovani. LXE408 fumarate has a low propensity to cross the blood brain barrier. LXE408 fumarate has the potential for visceral leishmaniasis (VL) research.

Antileishmanial agent-8 (compound 18) exhibits potent and selective activity against Leishmania donovani (L. donovani) with an IC50 of 5.64 μM and relatively low cytotoxicity in L-6 cells with an IC50 of 73.9 μM [1].

Antileishmanial agent-9 (compound 16c) exhibits potent and selective activity against Leishmania donovani (L. donovani) with an IC50 value of 4.01 μM, while demonstrating relatively low cytotoxicity in L-6 cells with an IC50 value of 40.1 μM [1].

Antileishmanial agent-7 (compound 23) exhibits potent antileishmanial activity against Leishmania donovani with an IC50 of 6.89 μM and against L-6 with an IC50 of 259 μM [1].

Antileishmanial agent-6 is a potent anti-leishmanial agent with anti-leishmanial activity (IC50: 0.54 μM) and cytotoxicity (IC50: 10.2 μM) against Leishmania donovani and L-6.

1. Harpagide has antibacterial activity. 2. Harpagide has antiviral activity. 3. Harpagide has anti-inflammatory activity.

3-Oxobetulin acetate is a derivative of the cholesterol biosynthesis inhibitor betulin. It inhibits the growth of P388 murine lymphocytic leukemia cells (EC50 = 0.12 µg/ml), as well as human MCF-7 breast, SF-268 CNS, H460 lung, and KM20L2 colon cancer cells (GI50s = 8, 10.6, 5.2, and 12.7 µg/ml, respectively), but not BxPC-3 pancreas or DU145 prostate cancer cells (GI50s = >10 µg/ml for both). 3-Oxobetulin acetate inhibits replication of X4 tropic recombinant HIV (NL4.3-Ren) in MT-2 lymphoblastoid cells (IC50 = 13.4 µM). It is also active against L. donovani amastigotes when used at a concentration of 50 µM.

Antileishmanial agent-14, a sulfuretin analog, exhibits potential activity against Leishmania donovani promastigotes (IC 50 = 4.1 μM) and inhibits infection by L. donovani amastigotes (IC 50 = 11.1 μM) [1].

Antiparasitic agent-18 (compound 3a) exhibits potent and selective antiprotozoal activity, effectively inhibiting T. brucei (EC50 = 0.4 µM), T. cruzi (EC50 = 0.21 µM), and L. donovani (EC50 = 0.26 µM) [1].

Compound F27 (Antileishmanial agent-19) is an antileishmanial compound effective against L. donovani promastigotes, demonstrating an IC50 of 3.39 μM. It functions by inhibiting the Leishmania prolyl-tRNA synthetase and disrupting the host PI3K/Akt/CREB axis-mediated IL-10 secretion. Additionally, Compound F27 promotes autophagy-mediated apoptosis in L. donovani promastigotes and has been shown to reduce parasite burden in L.d-infected animals [1].

Topoisomerase I Inhibitor 9 (compound 3d), a specific inhibitor of leishmanial topoisomerase IB, exhibits antileishmanial activity, demonstrating an IC50 value of 34.81μM against L. donovani promastigotes [1].

Compound 13, a topoisomerase I inhibitor 10, selectively inhibits leishmanial topoisomerase IB and exhibits antileishmanial activity. Specifically, it demonstrates efficacy against L. donovani promastigotes with an IC50 value of 27.91 μM [1].