The effects of trans-chalcone and chalcone 4 hydrate on the growth of Babesia and Theileria

Batiha, Gaber El-Saber and Beshbishy, Amani Magdy and Tayebwa, Dickson Stuart and Adeyemi, O. S. and Shaheen, Hazem and Yokoyama, Naoaki and Igarashi, Ikuo (2019) The effects of trans-chalcone and chalcone 4 hydrate on the growth of Babesia and Theileria. Neglected Tropical Diseases, 13 (5). pp. 1-18.

Text journal.pntd.0007030.pdf - Accepted Version Download (2MB)

Abstract

BackgroundChemotherapyis a principletoolforthecontrolandpreventionof piroplasmosis.Thesearchfora newchemotherapyagainstBabesiaandTheileriaparasiteshasbecomeincreasinglyurgentdueto thetoxicsideeffectsof anddevelopedresistanceto thecurrentdrugs.Chal-coneshaveattractedmuchattentiondueto theirdiversebiologicalactivities.Withtheaimtodiscovernewdrugsanddrugtargets,in vitroandin vivoantibabesialactivityoftrans-chal-cone(TC)andchalcone4 hydrate(CH)aloneandcombinedwithdiminazeneaceturate(DA),clofazimine(CF)andatovaquone(AQ)wereinvestigated.Methodology/PrincipalfindingsThefluorescence-basedassaywasusedforevaluatingtheinhibitoryeffectof TCandCHonfourBabesiaspecies,includingB.bovis,B.bigemina,B.divergens,B.caballi,andT.equi,thecombinationwithDA,CF,andAQonin vitrocultures,andonthemultiplicationof aB.microti–infectedmousemodel.Thecytotoxicityof compounds wastestedonMadin–Darbybovinekidney(MDBK),mouseembryonicfibroblast(NIH/3T3),andhumanforeskinfibroblast(HFF)celllines.Thehalfmaximalinhibitoryconcentration(IC50) valuesof TCandCHagainstB.bovis,B.bigemina,B.divergens,B.caballi,andT.equiwere69.6±2.3,33.3±1.2,64.8±2.5,18.9±1.7,and14.3±1.6μMand138.4±4.4,60.9±1.1,82.3±2.3,27.9±1.2,and19.2±1.5μM,respectively.In toxicityassays,TCandCHaffectedtheviabil-ityof MDBK,NIH/3T3,andHFFcelllinesthewithhalfmaximumeffectiveconcentration(EC50) valuesof 293.9±2.9,434.4±2.7,and498±3.1μMand252.7±1.7,406.3±9.7,and466±5.7μM,respectively.In themouseexperiment,TCreducedthepeakparasitemiaofB.microtiby71.8%whenadministeredintraperitoneallyat 25mg/kg.Combination therapiesof TC–DAandTC–CFweremorepotentagainstB.microtiinfectionin micethantheirmonotherapies.Conclusions/SignificanceIn conclusion,bothTCandCHinhibitedthegrowthofBabesiaandTheileriain vitro,andTCinhibitedthegrowthofB.microtiin vivo.Therefore,TCandCHcouldbecandidatesforthetreatmentof piroplasmosisafterfurtherstudies.

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