An abietane diterpene from Salvia cuspidata and some new derivatives are active against Trypanosoma cruzi

Lozano, Esteban; Spina, Renata; Tonn, Carlos E.; Sosa, Miguel A. Gama; Cifuente, Diego Alberto

doi:10.1016/j.bmcl.2015.10.082

Cited by 16 publications

(14 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, serratol (Schmidt et al, 2011), hypoestenonols A/B (Al , and diterpenes from some Vietnamese corals (Thao et al, 2015) were found to act against Trypanosoma brucei). Additionally, a number of other diterpenes (Alves et al, 1995;Freiburghaus et al, 1998;Batista et al, 1999;Scio et al, 2003;Uchiyama et al, 2003;Torres-Mendoza et al, 2004;Rubio et al, 2005;González et al, 2006;Sanchez et al, 2006;Ambrósio et al, 2008;Sartorelli et al, 2010;Izumi et al, 2012;Ramírez-Macías et al, 2012;Lozano et al, 2012b;Siless et al, 2013;Bou et al, 2014;Olmo et al, 2015;Lozano et al, 2015;Lozano et al, 2016) are also reported to act against T. cruzi.…”

Section: Resultsmentioning

confidence: 99%

Diterpenes as lead molecules against neglected tropical diseases

et al. 2016

View full text Add to dashboard Cite

Nowadays, neglected tropical diseases (NTDs) are reported to be present everywhere. Poor and developing areas in the world have received great attention to NTDs. Drug resistance, safety profile, and various challenges stimulate the search for alternative medications. Plant-based drugs are viewed with great interest, as they are believed to be devoid of side effects. Diterpenes, a family of essential oils, have showed attractive biological effects. A systematic review of the literature was carried out to summarize available evidences of diterpenes against NTDs. For this, databases were searched using specific search terms. Among the 2338 collected reports, a total of 181 articles were included in this review. Of them, 148 dealt with investigations using single organisms, and 33 used multiple organisms. No mechanisms of action were reported in the case of 164 reports. A total of 93.92% were related to nonclinical studies, and 4.42% and 1.66% dealt with preclinical and clinical studies, respectively. The review displays that many diterpenes are effective upon Chagas disease, chikungunya, echinococcosis, dengue, leishmaniasis, leprosy, lymphatic filariasis, malaria, schistosomiasis, and tuberculosis. Indeed, diterpenes are amazing drug candidates against NTDs. Copyright © 2016 John Wiley & Sons, Ltd.

show abstract

Section: Resultsmentioning

confidence: 99%

Diterpenes as lead molecules against neglected tropical diseases

et al. 2016

View full text Add to dashboard Cite

show abstract

“…All of the examples showed no mammalian activity up to 15 M in Vero cells, although this is a low maximum threshold level. 64 Even the simple anthraquinone damnacanthal (19) showed moderate activity against T. cruzi intracellular amastigotes with an EC50 value of 39.5 M but having a low selectivity with a SI value of 0.79. 65 In vivo studies were carried out investigating the antimalarial activity of 20.…”

Section: Quinonesmentioning

confidence: 99%

“…Compound 64 showed activity against T. brucei with an EC50 value of 5 M and an SI of >20 compared to J744.1 macrophages, but no activity against L. major promastigote cells. Plakortide E (64) has been shown to be a non-competitive, reversible inhibitor of the trypanosomatid cysteine protease, rhodesain, in addition to similar cysteine proteases from other species. 115 This suggests a similar mode of action for other endoperoxides, although further investigation into structure-activity relationships is required.…”

Section: Indole Alkaloidsmentioning

confidence: 99%

Active Natural Product Scaffolds against Trypanosomatid Parasites: A Review

Cockram

Smith

2018

J. Nat. Prod.

View full text Add to dashboard Cite

Neglected tropical diseases caused by trypanosomatid parasites are a continuing and escalating problem, which devastate the less economically developed cultures in countries in which they are endemic by impairing both human and animal health. Current drugs for these diseases are regarded as out-of-date, expensive, with unacceptable side-effects and mounting parasite resistance, meaning there is an urgent need for new therapeutics. Natural products have long been a source of potent, structurally diverse bioactive molecules. Herein are reviewed natural products with reported trypanocidal activity, which have been clustered based on core structural similarities, to aid the future discovery of new trypanocidal core motifs with potential routes to synthetically accessible natural product cores suggested.in both the New and Old Worlds, and these include L. amazonensis, L. major, L. infantum and L. donovani. The disease is transmitted via the bite of the female phlebotomine sand fly vector, with an estimated 300,000 new infections each year and over 1 billion people living in areas at risk, primarily throughout the tropics and subtropics. 10

show abstract

“…Abietane (12-hydroxy-11,14-diketo-6,8,12-abietatrien-19,20-olide) (HABTO) has been isolated from the aerial parts of Salvia cuspidata. This compound has a diterpene structure belonging to the abietane group (Lozano et al 2015) (Fig. 11.8).…”

Section: Diterpenesmentioning

confidence: 99%

Contribution of Microscopy for Understanding the Mechanism of Action Against Trypanosomatids

Lozano

Spina

Barrera

et al. 2018

Sesquiterpene Lactones

View full text Add to dashboard Cite

Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.

show abstract

An abietane diterpene from Salvia cuspidata and some new derivatives are active against Trypanosoma cruzi

Cited by 16 publications

References 22 publications

Diterpenes as lead molecules against neglected tropical diseases

Diterpenes as lead molecules against neglected tropical diseases

Active Natural Product Scaffolds against Trypanosomatid Parasites: A Review

Contribution of Microscopy for Understanding the Mechanism of Action Against Trypanosomatids

Contact Info

Product

Resources

About