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Article Publish Status: FREE
Abstract Title:

Effect of Harmine Alkaloid and Its-Methyl Derivatives Against.

Abstract Source:

Front Microbiol. 2021 ;12:716534. Epub 2021 Aug 5. PMID: 34421876

Abstract Author(s):

Maria L Alomar, Juan G Yañuk, Sergio O Angel, M Micaela Gonzalez, Franco M Cabrerizo

Article Affiliation:

Maria L Alomar

Abstract:

Toxoplasmosis is one of the most prevalent and neglected zoonotic global diseases caused by. The current pharmacological treatments show clinical limitations, and therefore, the search for new drugs is an urgent need in order to eradicate this infection. Due to their intrinsic biological activities,β-carboline (βC) alkaloids might represent a good alternative that deserves further investigations. In this context, theanti-activity of threeβCs, harmine (), 2-methyl-harminium (), and 9-methyl-harmine (), was evaluated herein. Briefly, the three alkaloids exerted direct effects on the parasite invasion and/or replication capability. Replication rates of intracellular treated tachyzoites were also affected in a dose-dependent manner, at noncytotoxic concentrations for host cells. Additionally, cell cycle analysis revealed that both methyl-derivativesandinduce parasite arrest in S/M phases. Compoundshowed the highest irreversible parasite growth inhibition, with a half maximal inhibitory concentration (IC50) value of 1.8± 0.2 μM and a selectivity index (SI) of 17.2 at 4 days post infection. Due to high replication rates, tachyzoites are frequently subjected to DNA double-strand breaks (DSBs). This highly toxic lesion triggers a series of DNA damage response reactions, starting with a kinase cascade that phosphorylates a large number of substrates, including the histone H2A.X to lead the early DSB marker γH2A.X. Western blot studies showed that basal expression of γH2A.X was reduced in the presence of. Interestingly, the typical increase inγH2A.X levels produced by camptothecin (CPT), a drug that generates DSB, was not observed when CPT was co-administered with. These findings suggest thatmight disruptDNA damage response.

Study Type : In Vitro Study

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