Susceptibility of Leishmania to novel pentavalent organometallics: Investigating impact on DNA and membrane integrity in antimony(III)-sensitive and -resistant strains.

The aim the present study was to investigate the impact of novel pentavalent organobismuth and organoantimony complexes on membrane integrity and their interaction with DNA, activity against Sb(III)-sensitive and -resistant Leishmania strains and toxicity in mammalian peritoneal macrophages. Ph3M(L)2 type complexes were synthesized, where M = Sb(V) or Bi(V) and L = deprotonated 3-(dimethylamino)benzoic acid or 2-acetylbenzoic acid. Both organobismuth(V) and organoantimony(V) complexes exhibited efficacy at micromolar concentrations against Leishmania amazonensis and L. infantum but only the later ones demonstrated biocompatibility. Ph3Sb(L1)2 and Ph3Bi(L1)2 demonstrated distinct susceptibility profiles compared to inorganic Sb(III)-resistant strains of MRPA-overexpressing L. amazonensis and AQP1-mutated L. guyanensis. These complexes were able to permeate the cell membrane and interact with the Leishmania DNA, suggesting that this effect may contribute to the parasite growth inhibition via apoptosis. Taken altogether, our data substantiate the notion of a distinct mechanism of uptake pathway and action in Leishmania for these organometallic complexes, distinguishing them from the conventional inorganic antimonial drugs.

Biomedical Applications of Green Synthesized Zinc Oxide and Magnesium-Doped Zinc Oxide Nanoparticles Using Aqueous Extract of Ziziphus Oxyphylla Leaves.

Zinc oxide (ZnO) and magnesium-doped zinc oxide (Mg-doped ZnO) nanoparticles (NPs) were synthesized using Ziziphus oxyphylla 's aqueous leaf extract as reducing agent. UV-Vis absorption peaks at 324 nm and 335 nm were indicative of ZnO and Mg-doped ZnO, respectively. FTIR absorption bands observed at 3238, 1043, 1400, 1401, 2186 and 2320 cm -1 suggested the presence of phenols, alcohols, saturated hydrocarbons, and possibly alkynes. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy revealed pure, spherical and agglomerated NPs with average size of 35.9 nm (ZnO) and 56.8 nm (Mg-doped ZnO). Both NPs remained active against all bacterial strains with the highest inhibition zones observed against Proteus vulgaris (21.16±1.25 mm for ZnO and 24.1±0.76 mm for Mg-doped ZnO. EtBr fluorescence (cartwheel assay) indicated efflux pump blockage, suggesting its facilitation in the bacterial growth inhibition. Antioxidant potential, determined via DPPH radical scavenging assay, revealed stronger antioxidant potential for Mg-doped ZnO (IC [Formula: see text]/mL) than pure ZnO (IC [Formula: see text]/mL). Furthermore, both NPs showed antileishmanial activity against Leishmania tropica promastigotes (IC [Formula: see text]/mL for Mg-doped ZnO and 64.34±6.56 for ZnO), while neither NP exhibited significant hemolysis, indicating biocompatibility and further assessment for their drugability.