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• Euphorbia wallichii carry high antileishmanial potentials. • Euphorbia wallichii kills Leishmania cells via membrane permeability and apoptosis. • Euphorbia wallichii carry low cytotoxicity to human blood erythrocytes. Clinically available synthetic chemotherapeutics to treat the vector-borne protozoan infection, leishmaniasis, are associated with serious complications such as toxicity and emergence of resistance. Natural products from plants consist of interesting biomolecules that may interfere with DNA or membrane integrity of the parasite and can possibly minimise the associated side effects. In the present study, various fractions of Euphorbia wallichii (EW) root extracts including n-hexane (EWNX), ethyl acetate (EWEA), chloroform (EWCH) and aqueous (EWAQ), were evaluated for their antileishmanial potential against Leishmania tropica followed by investigation of the possible mechanism of action via reactive oxygen species (ROS) quantification, membrane permeability (via sytox green dye) and apoptotic assay (via AO/EB method) using fluorescent microscopy. Two of the fractions i.e. EWEA and EWAQ inhibited the growth of promastigotes (IC 50 7.8 and 10.2 μg/mL, respectively) and amastigotes (IC 50 9.9 and 13.3 μg/mL, respectively) forms almost at similar concentrations as found for the standard antileishmanial drugs, tartar emetic (TA) and Glucantime (IC 50 9.4 and 21.5 μg/mL, respectively). Both the active fractions remained non-toxic towards human blood erythrocytes and were able to cause membrane permeability and apoptotic induction (using Triton X-100 as a positive control) leading to death of Leishmania parasites. However, both the fractions could not triger significant and persistent ROS generation, compared to hydrogen peroxide used as a positive control. Antilesihmanial activity of the two active fractions might be attributed to the presence of high quantity of tannins and saponins. [ABSTRACT FROM AUTHOR]

Novel organobismuth(V) and organoantimony(V) complexes of Ph 3 ML 2 type were synthesized, in which L = deprotonated 2-acetylbenzoic acid (2AcBH), 4-acetylbenzoic acid (4AcBH) or 5-acetylsalicylic acid (5AcSH) and M = bismuth(V) or antimony(V). Complexes [Ph 3 Bi(2AcB) 2 ] ( 1 ) [Ph 3 Sb(4AcB) 2 ] ( 2 ), [Ph 3 Bi(4AcB) 2 ] ( 3 ) and [Ph 3 Sb(5AcS) 2 . CHCl 3 ] ( 4 ) were characterized by elemental analysis, IR, and NMR. Crystal structures of 2 and 4 were determined by single crystal X-ray diffraction. In vitro cytotoxic activities against cancerous (human chronic myelogenous leukemia, K562 and murine metastatic melanoma, B16F10) and healthy non-cancerous (murine fibroblasts, L929 and murine melanocytes, Melan-A) cells showed that, compared to free ligands, both of the metal complexes are more active as anticancer agents at low concentration in cancerous cell lines, but also possessed toxic effect at comparatively higher concentration towards the non-cancerous cells. The organobismuth(V) complex Ph 3 Bi(2AcB) 2 was found to be more active than the Ph 3 BiCl 2 metal precursor against the tumor cell lines and exhibited the highest selectivity index. Moreover, evaluation of the pro-apoptotic activity of Ph 3 Bi(2AcB) 2 in B16F10 cells, by quantifying the cellular DNA using flow cytometry, indicates that cell cycle arrest and cell apoptosis contribute to the drug cytotoxicity. This work supports the great potential of organobismuth(V) dicarboxylate complexes as anticancer agents. [ABSTRACT FROM AUTHOR]

The antileishmanial drugs presently available have stern limitations regarding efficiency, safety and cost that make it crucial to hunt for novel therapeutic approaches from natural products. In current study crude methanolic extracts (CMEs) of four medicinally important plants were evaluated for their phytochemical constituents, antioxidant potentials, cytotoxicity and antileishmanial activities. Digera muricata (L) and Cannabis sativa (Linn) showed highest total phenolic and flavonoid content (273.4 μg GAE/mg DW and 206.8 μg QA/mg DW, respectively), amongst others. Total antioxidant capacity determined in vitro by phosphomolybdenum assay exhibited that Saccharum spontaneum (L) and Mangifera indica (L) were the strongest antioxidants (∼108 and ∼100 μg AAE/g of DW, respectively) plants amongst other tested. The S. spontaneum showed remarkable scavenging activity (EC 50 44.9 μg/mL), while M. indica showed to possess the lowest scavenging activity (EC 50 105.7 μg/mL) on 1,1-diphenyl-2-picrylhydrazyl. S. spontaneum and C. sativa were the least toxic (CC 50, 113.0 and 109.4 μg/mL respectively), while M. indica remained the most toxic (CC 50 42.46 μg/mL). Moreover, the in vitro evaluation of antileishmanial potential of plants CMEs, demonstrated a dose-dependent growth inhibition of L. major promastigotes and axenic amastigotes. M. indica and D. muricate extracts exhibited to possess antileishmanial potential at minute concentrations (IC 50 5.2 and 18.9 μg/mL, respectively) comparable to that of tartar emetic (IC 50 4.7μg/mL) against L. major promastigotes. Each CME was significantly active (p < 0.0001) against L. major axenic amastigotes when compared to Glucantime®. This study encourages the isolation of bioactive compounds from these plants for antileishmanial drug development. [ABSTRACT FROM AUTHOR]