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005			20250626090915.0
040			_cCICY
090			_aB-21680
245	1	0	_aNaphthoquinones and derivatives for chemotherapy: perspectives and limitations of their anti-trypanosomatids activities
490	0		_aCurrent Pharmaceutical Design, 27(15), p.1807-1824, 2021
500			_aArtículo
520	3		_aChagas disease, Sleeping sickness and Leishmaniasis, caused by trypanosomatids Trypanosoma cruzi, Trypanosoma brucei and leishmania spp., respectively, are considered neglected tropical diseases, and they especially affect impoverished populations in the developing world. The available chemotherapies are very limited, and a search for altematives is still necessary. In folk medicine, natural naphthoquinones have been employed for the treatment of a great variety of illnesses, including parasitic infections. This review is focused on the anti-trypanosomatid activity and mechanistic analysis of naphthoquinones and derivatives. Among ali the series of derivatives tested in vitro, naphthoquinone-derived 1,2,3-triazoles were very active on T. cruzi infective forms in blood bank conditions, as well as in amastigotes of Leishmania spp. naphthoquinones containing a CF, on a phenyl amine ring inhibited T. brucei proliferation in the nano molar range, and naphthopterocarpanquinones stood out for their activity on a range of leishmania species. Sorne of these compounds show.ed a promising selectivity index (SI) (30 to 1900), supporting further analysis in animal models. lndeed, high toxicity to the host and inactivation by blood components are crucial obstacles to be overcome to use naphthoquinones and/or their derivatives for chemotherapy. Multidisciplinary initiatives embracing medicinal chemistry, bioinformatics, biochemistry, and molecular and cellular biology need to be encouraged to allow the optimization of these compounds. Large scale automated tests are pivotal for the efficiency of the screening step, and subsequent evaluation of both the mechanism of action in vitro and pharmacokinetics in vivo is essential for the development of a novel, specific and safe derivative, minimizing adverse effects.
650	1	4	_aT. CRUZI
650	1	4	_aLEISHMANIA SPP.
650	1	4	_aT. BRUCEI
650	1	4	_aCHAGAS DISEASE
650	1	4	_aLEISHMANIASIS
650	1	4	_aSLEEPING SICKNESS
650	1	4	_aCHEMOTHERAPY
650	1	4	_aNAPHTHOQUINONES
650	1	4	_aNAPHTHOIMIDAZOLES
700	1	2	_aDantas-Pereira, L.
700	1	2	_aCunha-Junior, E. F.
700	1	2	_aAndrade-Neto, V. V.
700	1	2	_aBower, J. F.
700	1	2	_aJardim, G. A.
700	1	2	_ada Silva Júnior, E. N.
700	1	2	_aMenna-Barreto, R. F.
856	4	0	_uhttps://drive.google.com/file/d/1-dVhXwmNViTgnvSY-k_SGPjFpMAIJph8/view?usp=drive_link _zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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