Parasitic diseases pose significant health, social, and economic challenges, particularly in tropical regions [1-5]. Protozoan parasites, including Trypanosoma cruzi, Leishmania mexicana, Plasmodium falciparum, Giardia intestinalis, and Trichomonas vaginalis, are primary culprits behind these diseases. Protozoan infections contribute significantly to global mortality and morbidity, impacting over 500 million individuals worldwide. The burden of protozoan diseases is on the rise globally, exacerbated by the ineffectiveness of current antiprotozoal medications due to drug resistance and toxicity issues [3]. Consequently, there is a pressing need for novel drugs targeting protozoan parasites [3-8].
In response to this need, the Life Chemicals team has developed a proprietary Antiprotozoal Screening Library, comprising more than 8,200 small-molecule screening compounds. These compounds hold promise for combatting major protozoan diseases such as giardiasis, leishmaniasis, malaria, trichomoniasis, and trypanosomiasis.
The compound selection can be customized based on your requirements, cherry picking is available.
Please, contact us at orders@lifechemicals.com for any additional information and price quotations.
Compound selection
The Life Chemicals HTS Compound Collection was screened against a reference set of over 5,000 compounds known to exhibit activity against dangerous protozoa. This reference set was curated using data from reputable inhibitor databases such as the ChEMBL and BindingDB, with reported inhibitory activity below 10 μM as determined by bioassays. A 2D fingerprint similarity search was conducted, comparing the reference set to the proprietary HTS Compound Collection, with a Tanimoto similarity index threshold set at > 0.8. Additionally, in-house medicinal chemistry filters were applied to exclude compounds containing Pan Assay Interference Compounds (PAINS) and toxicophores.
As a result, over 8,200 drug-like screening compounds with potential antiprotozoal activity were identified and included in the protozoa-focused Screening Set. The comprehensive list of targeted protozoa families and species is presented below:
- Cryptosporidium parvum
- Entamoeba histolytica
- Giardia (G.intestinalis)
- Leishmania (L.amazonensis, L.braziliensis, L.chagasi, L.donovani, L.major)
- Plasmodium (P.berghei, P.falciparum)
- Schistosoma mansoni
- Toxoplasma gondii
- Trichomonas vaginalis
- Trypanosoma brucei (T.brucei (brucei & rhodesiense)
- Trypanosoma cruzi (normal & strain CL Brener)
The HTS Compound Collection was subsequently scrutinized for close analogs of molecules with established activity against various protozoa-related protein targets, using an 80% similarity cut-off (Tanimoto) on MDL public keys fingerprints. As a result, compounds for the following molecular targets were selected:
- Cannabinoid CB1 receptor
- Carbonic anhydrase I and II
- Cathepsin L endopeptidase
- Cdc2-related kinase
- Cruzipain cysteine protease
- Falcipain 2 cysteine protease
- Glutamate NMDA receptor
- Glyceraldehyde-3-phosphate dehydrogenase
- Ser/thr-protein kinase Aurora-B
- Sterol 14-alpha demethylase
Representative screening compounds from the Antiprotozoal Screening Compound Library
References:
- Nash TE. Parasitic Diseases that Cause Seizures. Epilepsy Curr. 2014 Jan;14(1 Suppl):29-34.
- Renslo, A., McKerrow, J. Drug discovery and development for neglected parasitic diseases. Nat Chem Biol 2, 2006, 701–710.
- Lee, S.-M., Kim, M.-S., Hayat, F., Shin, D. Recent Advances in the Discovery of Novel Antiprotozoal Agents. Molecules 2019, 24, 3886.
- Thurston S, Hite GL, Petry AN, Ray SD. Antiprotozoal Drugs. Side Effects of Drugs Annual. 2015;37:321-327.
- https://www.drugoffice.gov.hk/eps/do/en/consumer/news_informations/dm_20.html
- Mahmoud AB, Danton O, Kaiser M, et al. Lignans, Amides, and Saponins from Haplophyllum tuberculatum and Their Antiprotozoal Activity. Molecules. 2020;25(12):2825.
- Müller J, Hemphill A. Drug target identification in protozoan parasites. Expert Opin Drug Discov. 2016;11(8):815-824.
- Pertino MW, Vega C, Rolón M, Coronel C, Rojas de Arias A, Schmeda-Hirschmann G. Antiprotozoal Activity of Triazole Derivatives of Dehydroabietic Acid and Oleanolic Acid. Molecules. 2017;22(3):369.
- Iris Dawn Tabangcora. Antiprotozoal Drugs. https://nurseslabs.com/antiprotozoal-drugs