000079553 001__ 79553
000079553 005__ 20200716101427.0
000079553 0247_ $$2doi$$a10.1128/AAC.02373-18
000079553 0248_ $$2sideral$$a111226
000079553 037__ $$aART-2019-111226
000079553 041__ $$aeng
000079553 100__ $$0(orcid)0000-0001-6140-2423$$aMachicado, C.
000079553 245__ $$aScreening the Pathogen Box for Identification of New Chemical Agents with Anti-Fasciola hepatica Activity
000079553 260__ $$c2019
000079553 5060_ $$aAccess copy available to the general public$$fUnrestricted
000079553 5203_ $$aFascioliasis is an infectious parasitic disease distributed globally and caused by the liver fluke Fasciola hepatica or F. gigantica. This neglected tropical disease affects both animals and humans, and it represents a latent public health problem due to the significant economic losses related to its effects on animal husbandry. For decades, triclabendazole has been the unique anti-Fasciola drug that can effectively treat this disease. However, triclabendazole resistance in fascioliasis has more recently been reported around the world, and thus, the discovery of novel drugs is an urgent need. The aim of this study was to investigate the fasciocidal properties of 400 compounds contained in the Pathogen Box. The first stage of the screening was carried out by measuring the fasciocidal activity on metacercariae at a concentration of 33 mu M each compound (the standard dose). Subsequently, the activities of the most active compounds (n = 33) at their 50% inhibitory concentration (IC50) values against metacercariae were assayed, and the results showed that 13 compounds had IC(50)s of <= 10 mu M. The second stage queried the activities of these compounds at 33 mu M against adult flukes, with seven of the compounds producing high mortality rates of >50%. Four hit compounds were selected on the basis of their predicted nontoxic properties, and the IC50 values obtained for adult worms were <10 mu M; thus, these compounds represented the best fasciocidal compounds tested here. A cytotoxicity assay on four types of cell lines demonstrated that three compounds were nontoxic at their most active concentration. In conclusion, three hit compounds identified in this proof-of-concept study are potential candidates in the discovery of new fasciocidal drugs. Further studies are warranted.
000079553 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000079553 590__ $$a4.904$$b2019
000079553 592__ $$a2.135$$b2019
000079553 591__ $$aPHARMACOLOGY & PHARMACY$$b28 / 270 = 0.104$$c2019$$dQ1$$eT1
000079553 593__ $$aInfectious Diseases$$c2019$$dQ1
000079553 591__ $$aMICROBIOLOGY$$b28 / 134 = 0.209$$c2019$$dQ1$$eT1
000079553 593__ $$aPharmacology (medical)$$c2019$$dQ1
000079553 593__ $$aPharmacology$$c2019$$dQ1
000079553 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000079553 700__ $$aSoto, M.P.
000079553 700__ $$aTimoteo, O.
000079553 700__ $$aVaisberg, A.
000079553 700__ $$aPajuelo, M.
000079553 700__ $$aOrtiz, P.
000079553 700__ $$aMarcos, L.A.
000079553 773__ $$g63, 3 (2019), e02373-18[13pp]$$pAntimicrob. agents chemother.$$tAntimicrobial Agents and Chemotherapy$$x0066-4804
000079553 8564_ $$s584789$$uhttps://zaguan.unizar.es/record/79553/files/texto_completo.pdf$$yPostprint
000079553 8564_ $$s52734$$uhttps://zaguan.unizar.es/record/79553/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000079553 909CO $$ooai:zaguan.unizar.es:79553$$particulos$$pdriver
000079553 951__ $$a2020-07-16-08:45:49
000079553 980__ $$aARTICLE