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In vitro trypanocidal activity of Helenalin and Hymenin derivativesMaría F.Beer1, 2, Augusto Bivona3,Natacha Cerny3,Silvia I.Cazorla3 ,Emilio Malchiodi3,Virginia S. Martino2,Carlos E.Tonn1,Osvaldo J. Donadel1,Valeria P. Sülsen2. 1INTEQUI-CONICET, (UNSL-CONICET) Facultad de Química, Bioquímica y Farmacia.Chacabuco y Pedernera, San Luis, CP: 5700, Argentina. 2IQUIMEFA(UBA-CONICET), Facultad de Farmacia y Bioquímica, Junín 956 2do piso, CABA, Argentina. 3 Cátedrade Inmunología, IDEHU (CONICET-UBA), Facultad de Farmacia y Bioquímica, BuenosAires, Argentina and Instituto de Microbiología y Parasitología Médica, IMPaM(CONICET-UBA),Facultad de Medicina, Buenos Aires, Argentina, 1113.* Corresponding Author?s E-mail (vsulsen@ffyb.uba.ar)Parasitic diseases such as Chagas´ disease, affect millions of people mainly in developing countries. This parasitosis is part of a group of diseasesconsidered neglected, abandoned and poverty-related. According to the World Health Organization 6-7 million people are infected with Trypanosoma cruzi, the etiological agent of Chagas´ disease [1]. Drugs availableto treat this protozoan disease, nifurtimox and benznidazol, have limitations dueto adverse effects and lack of effectively.Natural products play an important role in the discovery and development of new drugs.Many natura!compounds and its derivativesare used in current chemotherapy.lt is noteworthy that sorne semisynthetic compounds derived from a natural framework sometimes impróve the biological activity respect the originalnatural productor enhanceits biodisponibility. Sesquiterpene ladones (STLs) are a group of natural terpenoids with a wide range of biological activities, beingantiparasitic and antitumor among the most relevant. The STL artemisinin and its semi-synthetic derivatives are used nowadaysin combination therapiesfor the treatment of malaria.!n this sense, the aim of the present work was to obtain derivatives from the STLs helenalinand hymeninand furtherevaluate their activity on Trypanosoma cruzi.From the STL helenalin, isolated from Gail/ardia megapotamica (Asteraceae), the corresponding acetate and a silyl derivative, obtainedwith dimethylisopropylchlorosilane (DMIPSCI), were synthesized. The STL hymenin was isolatedfrom Partheniumhysterophorus (Asteraceae). The corresponding analogue of this STL withtrimethylchlorosilane (TMSCI) wassynthetized . Both helenalin and hymenin and its derivatives were evaluated againstT. cruzi epimastigotes (RA)by a [3H]-thymidine uptake assay.Helenalin and its derivativeswere active against epimastigotes with IC50 valu es of 6.3, 0.9 (acetate) and 1.1 (Jg/ml (DMIPSCIderivative), respectively.Hymenin and its TMSCI derivative showed trypanocidal activity with IC50 of 2..1 and 2..5 µg/ml, respectively .Both acetateand DMIPSCl helenalin derivatives showed higher activity than the natural compound. Besides,both hymenin and its analogue presented similarIC50 values. Chemical modification of natural compounds is a strategy to enhancethe activityand reduce toxic effects. The cyt0;toxicity of the compounds on mammalian cells will be evaluated in order to determine their selectivity ofaction.: The a;sessment of their activity against trypomastigote and amastigote forms of the parasite wi!!also be performed. Keywords: sesquiterpene lactone, Trypanosoma cruzi, derivatives Acknowledgements: This work was supported by grants from PICT 1753 (2012-2015) (The NationalAgency for Science and Technology Promotion), PIP 0324 (National Scientific andTechnica/ Research Counci/), and UBACYT 20020130200270 (University of BuenosAires). References[1) World Health Organ ization 2.016. Factsheet Chagas disease (American trypanosomiasis). http://www.who.int/mediacentre/factsheets/fs:340/en/. AccessedAugust 2.016.