Abstract
Background: Neglected tropical diseases are a group of infections caused by microorganisms and viruses that affect mainly poor regions of the world. In addition, most available drugs are associated with long periods of treatment and high toxicity which limits the application and patient compliance. Investment in research and development is not seen as an attractive deal by the pharmaceutical industry since the final product must ideally be cheap, not returning the amount invested. Natural products have always been an important source for bioactive compounds and are advantageous over synthetic compounds when considering the unique structural variety and biological activities. On the other hand, isolation difficulties and low yields, environmental impact and high cost usually limit their application as drug per se.
Objective: In this review, the use of natural products as prototypes for the semi-synthesis or total synthesis, as well as natural products as promising hits is covered, specifically regarding compounds with activities against trypanosomatids such as Trypanosoma spp. and Leishmania spp. Methods: Selected reports from literature with this approach were retrieved. Conclusion: As summary, it can be concluded that natural products are an underestimated source for designing novel agents against these parasites.Keywords: Natural products, neglected diseases, prototypes, semi-synthetic derivatives, synthetic derivatives, trypanosomatids.
[http://dx.doi.org/10.1016/j.jep.2005.06.006] [PMID: 16023811]
[http://dx.doi.org/10.1016/j.jep.2006.01.007] [PMID: 16459039]
[http://dx.doi.org/10.1016/j.cell.2015.11.031] [PMID: 26638061]
[http://dx.doi.org/10.1016/j.procbio.2010.09.004]
[http://dx.doi.org/10.1016/j.bej.2012.01.006] [PMID: 23180977]
[http://dx.doi.org/10.1007/s13659-017-0125-y] [PMID: 28421410]
[http://dx.doi.org/10.1055/s-0042-112031] [PMID: 27442262]
[http://dx.doi.org/10.1080/14786419.2016.1180604] [PMID: 27154232]
[http://dx.doi.org/10.3109/13880209.2016.1150304] [PMID: 26983579]
[http://dx.doi.org/10.4103/0974-8520.100295] [PMID: 23049178]
[http://dx.doi.org/10.1590/0074-0276140362] [PMID: 25466622]
[http://dx.doi.org/10.2174/187152507781058726] [PMID: 17630949]
[http://dx.doi.org/10.3389/fmicb.2012.00283] [PMID: 22888328]
[http://dx.doi.org/10.12688/f1000research.11120.1] [PMID: 28649370]
[http://dx.doi.org/10.1016/j.jaad.2014.08.051] [PMID: 26568335]
[http://dx.doi.org/10.1371/journal.pntd.0000313] [PMID: 18958165]
[http://dx.doi.org/10.1038/nrd4683] [PMID: 26435527]
[http://dx.doi.org/10.1038/513481a] [PMID: 25254460]
[http://dx.doi.org/10.3390/molecules19055761] [PMID: 24802987]
[http://dx.doi.org/10.1248/bpb.29.2307] [PMID: 17077535]
[http://dx.doi.org/10.1515/znc-2011-7-807] [PMID: 21950160]
[http://dx.doi.org/10.1021/np300638f] [PMID: 23167812]
[http://dx.doi.org/10.1016/j.bmcl.2011.01.101] [PMID: 21474310]
[http://dx.doi.org/10.1055/s-0029-1185670] [PMID: 19431103]
[http://dx.doi.org/10.1016/j.phymed.2006.11.027] [PMID: 17291734]
[http://dx.doi.org/10.1016/j.phymed.2016.11.015] [PMID: 28160863]
[http://dx.doi.org/10.1002/cbdv.201500280] [PMID: 27251851]
[http://dx.doi.org/10.1016/j.exppara.2012.08.019] [PMID: 22981719]
[http://dx.doi.org/10.1016/j.bmcl.2016.01.040] [PMID: 26821820]
[http://dx.doi.org/10.1111/cbdd.12986] [PMID: 28371557]
[http://dx.doi.org/10.1055/s-2006-957548] [PMID: 9810278]
[http://dx.doi.org/10.1016/S0031-9422(03)00356-X] [PMID: 12943793]
[http://dx.doi.org/10.1016/j.ejmech.2017.01.029] [PMID: 28152426]
[http://dx.doi.org/10.1016/S0031-9422(99)00361-1] [PMID: 10643674]
[http://dx.doi.org/10.1021/np990255u] [PMID: 10514334]
[http://dx.doi.org/10.1002/cmdc.201000230] [PMID: 20575140]
[http://dx.doi.org/10.1021/np020308z] [PMID: 12542361]
[http://dx.doi.org/10.1016/j.bmcl.2015.05.022] [PMID: 26037321]
[http://dx.doi.org/10.1021/np070560c] [PMID: 18163590]
[http://dx.doi.org/10.1021/jm800812k] [PMID: 18798609]
[http://dx.doi.org/10.1080/14786419.2015.1030740] [PMID: 25880257]
[http://dx.doi.org/10.1055/s-0029-1185364] [PMID: 19241331]
[http://dx.doi.org/10.3390/ijms15058360] [PMID: 24823881]
[http://dx.doi.org/10.3390/molecules21091237] [PMID: 27649126]
[http://dx.doi.org/10.1016/j.fitote.2016.04.005] [PMID: 27083380]
[http://dx.doi.org/10.1021/np5006554] [PMID: 25314007]
[http://dx.doi.org/10.1016/j.phytochem.2016.11.008] [PMID: 27889243]