Sesquiterpene Lactones by Valeria Patricia Sülsen & Virginia Susana Martino

Author:Valeria Patricia Sülsen & Virginia Susana Martino
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

Recently, Rabito et al. (2014) have assessed the effect of the intramuscular injection of the STL-rich dichloromethane fraction of Tanacetum parthenium for 4 weeks to find a significant reduction (p = 0.0010) in the growth and size of footpad lesions in BALB/c mice infected with 1x107 L. amazonensis metacyclic promastigotes. It should be borne in mind that the main STLs present in the dichloromethane fraction are parthenolide and 11,13-dehydrocompressanolide.

The organic and aqueous extracts of Mikania micrantha, M. parodii, M. periplocifolia, and M. cordifolia were tested on L. braziliensis promastigotes (Laurella et al. 2012). The bioassay-guided fractionation of M. micrantha organic extract led to the identification of two active fractions. The chromatographic profile and infrared analysis of these fractions revealed the presence of STLs. At a concentration of 100 μg/ml, the organic extracts of M. micrantha and M. parodii displayed leishmanicidal activity with growth inhibition rates above 85%. At the lowest concentration tested (1 μg/ml), M. micrantha was the most active extract causing an inhibition of 77.8 ± 1.1%.

The antileishmanial activities of an STL-rich preparation—a leaf rinse extract (LRE) from Tithonia diversifolia—was tested against the main causative agent of MCL. Results revealed that LRE is a rich source of potent leishmanicidal compounds, with an IC50 value of 1.5 ± 0.50 μg/ml against L. braziliensis promastigotes (H3227 MHOM/BR/94/H-3227) originally isolated from a human case of MCL in the state of Ceará, Brazil. Therefore, eight STLs from the LRE were initially assessed for their leishmanicidal activity against L. braziliensis promastigotes. One of them did not present any significant leishmanicidal effect (IC50 > 50 μg/ml). Another STL had a cytotoxic effect on macrophages (4.5 μg/ml). Five leishmanicidal STLs with the highest level of selectivity were further evaluated against the intracellular parasites (amastigotes) using peritoneal macrophages. Tirotundin 3-O-methyl ether, tagitinin F, and a guaianolide were able to cause a significant reduction in the internalization of parasites after 48 h, as compared to the negative control (p < 0.05) (de Toledo et al. 2014).

Sosa et al. (2016) have evaluated 17 STLs, isolated from five species of the tribe Vernonieae, for their in vitro activity against L. amazonensis and L. braziliensis promastigotes. As all these natural compounds were found to have potent to mild antileishmanial properties, a quantitative structure-activity relationship study has also been performed. The most active compounds against L. braziliensis were isodeoxyelephantopin and deoxyelephantopin, which bear two lactone rings in their structure, showing IC50 values 1.45 μM and 1.34 μM, respectively, followed by a goyazensolide natural derivative, showing an IC50 value of 1.60 μM against L. amazonensis.

The efficacy of different STLs against Leishmania species causing both cutaneous and visceral forms has been reported. Two terpenoid metabolites, isoiguesterin and its analogue, 20-epi-isoiguesterinol, both isolated from Salacia madagascariensis (Celastraceae), have strong submicromolar leishmanicidal potency against both L. donovani and L. mexicana (IC50, 0.20 μM and 0.082 μM, respectively) (Thiem et al. 2005).

The combination therapy with antileishmanial drugs is currently considered as one of the most rational approaches to lower the treatment failure rate and to limit the spreading of drug resistance phenomena (Gazanion et al.

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