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Anti-protozoal activity of Thymol and a Thymol ester against Cryptosporidium parvum in cell culture.

ABSTRACT: Cryptosporidium parvum is a protozoan parasite that infects intestinal epithelial cells causing malabsorption and severe diarrhea. The monoterpene thymol has been reported to have antifungal and antibacterial properties but less is known about the antiparasitic effect of this compound. Terpenes are sometimes unsuitable for therapeutic and food applications because of their instability. Esterification of terpenes eliminates this disadvantage. The present study evaluates the effects of thymol (Th) and a thymol ester, thymol octanoate (TO), against C. parvum infectivity in vitro. The cytotoxicity IC₅₀ value for TO after 24 h of treatment was 309.6 ?g/mL, significantly higher than that of Th (122.5 ?g/mL) in a human adenocarcinoma cell line (HCT-8). In the same way, following 48 h of treatment, the cytotoxicity IC₅₀ value for TO was significantly higher (139 ?g/mL) than that of Th (75.5 ?g/mL). These results indicate that esterification significantly reduces Th cytotoxicity. Dose-dependent effects were observed for TO and Th when both parasite invasion and parasite growth assays were evaluated. When evaluated for their activity against C. parvum growth cultured in vitro in HCT-8 cells, the anti-cryptosporidial IC₅₀ values were 35.5 and 7.5 ?g/mL, for TO and Th, respectively. Together, these findings indicate that esterified thymol has anti-cryptosporidial effect comparable with its parental compound thymol, but with improved safety margins in mammalian cells and better physicochemical properties that could make it more suitable for diverse applications as an antiparasitic agent.

SUBMITTER: Dominguez-Uscanga A

PROVIDER: S-EPMC7932911 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Anti-protozoal activity of Thymol and a Thymol ester against Cryptosporidium parvum in cell culture.

Dominguez-Uscanga Astrid A Aycart Danielle Francesca DF Li Kun K Witola William H WH Andrade Laborde Juan E JE

International journal for parasitology. Drugs and drug resistance 20210218

Cryptosporidium parvum is a protozoan parasite that infects intestinal epithelial cells causing malabsorption and severe diarrhea. The monoterpene thymol has been reported to have antifungal and antibacterial properties but less is known about the antiparasitic effect of this compound. Terpenes are sometimes unsuitable for therapeutic and food applications because of their instability. Esterification of terpenes eliminates this disadvantage. The present study evaluates the effects of thymol (Th) ...[more]

PMID: 33647675

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Project description:BackgroundHundreds of millions of people are infected with cryptosporidiosis annually, with immunocompromised individuals suffering debilitating symptoms and children in socioeconomically challenged regions at risk of repeated infections. There is currently no effective drug available. In order to facilitate the pursuit of anti-cryptosporidiosis targets and compounds, our study spans the classification of the Cryptosporidium parvum kinome and the structural and biochemical characterization of representatives from the CDPK family and a MAP kinase.ResultsThe C. parvum kinome comprises over 70 members, some of which may be promising drug targets. These C. parvum protein kinases include members in the AGC, Atypical, CaMK, CK1, CMGC, and TKL groups; however, almost 35% could only be classified as OPK (other protein kinases). In addition, about 25% of the kinases identified did not have any known orthologues outside of Cryptosporidium spp. Comparison of specific kinases with their Plasmodium falciparum and Toxoplasma gondii orthologues revealed some distinct characteristics within the C. parvum kinome, including potential targets and opportunities for drug design. Structural and biochemical analysis of 4 representatives of the CaMK group and a MAP kinase confirms features that may be exploited in inhibitor design. Indeed, screening CpCDPK1 against a library of kinase inhibitors yielded a set of the pyrazolopyrimidine derivatives (PP1-derivatives) with IC₅₀ values of < 10 nM. The binding of a PP1-derivative is further described by an inhibitor-bound crystal structure of CpCDPK1. In addition, structural analysis of CpCDPK4 identified an unprecedented Zn-finger within the CDPK kinase domain that may have implications for its regulation.ConclusionsIdentification and comparison of the C. parvum protein kinases against other parasitic kinases shows how orthologue- and family-based research can be used to facilitate characterization of promising drug targets and the search for new drugs.

Dataset Information

Anti-protozoal activity of Thymol and a Thymol ester against Cryptosporidium parvum in cell culture.

Publications

Anti-protozoal activity of Thymol and a Thymol ester against Cryptosporidium parvum in cell culture.

Similar Datasets

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