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Cutaneous leishmaniasis is caused by protozoa of the genus Leishmania and spread by sandflies. The standard therapy for this ailment is the first-line medication of pentavalent antimonial and the second drug line of pentamidine amphotericin B. All are practiced over the years and exhibit adverse toxicity effects. Herbal product-derived medicine is a promising potential source for treating parasitic diseases. Xanthatin, a xanthanolide sesquiterpene lactone, is isolated from  Xanthium strumarium  L. treats several ailments in many countries. In the present study, we investigated the leishmanicidal activity of the xanthatin by using a metabolomics-based analysis in J774 macrophages and amastigotes phases in  Leishmania major . Xanthatin was isolated and identified by NMR spectroscopy. Macrophage toxicity of xanthatin performed by MTT assay. Macrophages infected by the L. major's promastigote stationary phase, the infection rate (IR), and multiplication index (MI) were calculated. Axenic amastigotes were treated with xanthatin. Cell quenching and metabolite extraction were performed, and the metabolome profile was analyzed with NMR spectroscopy. Outliers were classified by using multivariate statistical analysis software, and relevant metabolites and pathways were worked out. The xanthatin IC 50 rate defined 0.75 µg/mL base on macrophages viability and also  in-vitro  activity of xanthatin on amastigotes showed the best leishmanicidal activity in IR and MI values of 53% and 62.5%, respectively. Xanthatin altered amino sugars and nucleotide sugars metabolism, starch and sucrose metabolism, cyanoamino acid, and galactose metabolism. Our finding revealed that the main target of xanthatin is carbon metabolism, which is an essential step for amastigotes virulence., Competing Interests: The authors have no conflict of interest to declare.

A series of 2-amino-4-(nitroalkyl)-4H-chromene-3-carbonitriles were synthesized by an efficient multicomponent reaction in aqueous media using DBU as a catalyst at room temperature. Mild condition, environment friendly procedure and excellent yields are the main advantages of this procedure. The cytotoxic activity of target compounds were evaluated against three cancer cell lines MDA-MB-231, MCF-7 and T47D in comparison with etoposide as reference drug. Generally, all compounds showed good cell growth inhibitory activity with IC(50) values less than 30 μg/mL. Their activities were comparable or more potent than standard drug etoposide. The 6-bromo- derivatives 7e and 7f showed promising cytotoxic activity with IC50 values in the range of 3.46-18.76 μg/mL, being more potent than etoposide against all tested cell lines.