Reactive oxygen species generating photosynthesized ferromagnetic iron oxide nanorods as promising antileishmanial agent.

Aim: To investigate the photodynamic therapeutic potential of ferromagnetic iron oxide nanorods (FIONs), using Trigonella foenum-graecum as a reducing agent, against Leishmania tropica. Materials & methods: FIONs were characterized using ultraviolet visible spectroscopy, x-ray diffraction and scanning electron microscopy. Results: FIONs showed excellent activity against L. tropica promastigotes and amastigotes (IC50 0.036 ± 0.003 and 0.072 ± 0.001 µg/ml, respectively) upon 15 min pre-incubation light-emitting diode light (84 lm/W) exposure, resulting in reactive oxygen species generation and induction of cell death via apoptosis. FIONs were found to be highly biocompatible with human erythrocytes (LD50 779 ± 21 µg/ml) and significantly selective (selectivity index >1000) against murine peritoneal macrophages (CC50 102.7 ± 2.9 µg/ml). Conclusion: Due to their noteworthy in vitro antileishmanial properties, FIONs should be further investigated in an in vivo model of the disease.

Comprehensive investigation on the synergistic antibacterial activities of Jatropha curcas pressed cake and seed oil in combination with antibiotics.

Synergistic combinations of various antimicrobial agents are considered ideal strategies in combating clinical and multidrug resistant (MDR) infections. In this study, antibacterial potential of Jatropha curcas crude seed extracts, seed oil, commercially available antibiotics, and their combinations were investigated for their synergistic effect against clinical, MDR and ATCC bacterial strains by agar well diffusion assay. Methanolic extracts remained more active against Staphylococcus aureus (ATCC), with zone of inhibition (ZOI) of 21 mm, than clinical and methicillin-resistant S. aureus (MRSA) strains (ZOI range ~ 15.0-17.0 mm). Molecular docking demonstrated that beta-monolaurin from methanolic extract exhibited greater affinity conformation for UDP-N-acetylmuramoyl-tripeptide-D-alanyl-D-alanine (MurF) ligase's active pocket with binding energy of -7.3 kcal/mol. Moxifloxacin exhibited greater activity against Escherichia coli (ATCC) (ZOI ~ 50.0 mm), followed by ofloxacin against Pseudomonas chlororaphis (47.3 mm), moxifloxacin against P. monteilii (47 mm), P. aeruginosa (46.3 mm) and MRSA2 (46 mm) and ofloxacin against S. aureus (ATCC) strains (45.7 mm). Methanolic extract in combination with rifampicin showed the highest synergism against MRSA strains, A. baumannii, E. coli, E. faecalis, S. aureus, and P. aeruginosa, A. baumannii (MDR strain), P. chlororaphis, E. coli ATCC25922 and S. aureus ATCC25923. In combinations, moxifloxacin exhibited the highest antagonism. The methanolic, n-hexane, aqueous extracts and seed oil in various combinations with antibiotics showed 44.71, 32.94, 9.41 and 25.88% synergism, respectively. The current study showed that potency of antibiotics was improved when screened in combination with J. curcas seed's components, supporting the drug combination strategy to combat antibacterial resistance.

Cytotoxicity and apoptotic activity of novel organobismuth(V) and organoantimony(V) complexes in different cancer cell lines.

Novel organobismuth(V) and organoantimony(V) complexes of Ph3ML2 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 [Ph3Bi(2AcB)2] (1) [Ph3Sb(4AcB)2] (2), [Ph3Bi(4AcB)2] (3) and [Ph3Sb(5AcS)2(.)CHCl3] (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 Ph3Bi(2AcB)2 was found to be more active than the Ph3BiCl2 metal precursor against the tumor cell lines and exhibited the highest selectivity index. Moreover, evaluation of the pro-apoptotic activity of Ph3Bi(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.

Novel triphenylantimony(V) and triphenylbismuth(V) complexes with benzoic acid derivatives: structural characterization, in vitro antileishmanial and antibacterial activities and cytotoxicity against macrophages.

Two novel organoantimony(V) and two organobismuth(V) complexes of the type ML2 were synthesized, with L = acetylsalicylic acid (HL1) or 3-acetoxybenzoic acid (HL2) and M = triphenylantimony(V) (M1) or triphenylbismuth(V) (M2). Complexes, [M1(L1)2] (1), [M1(L2)2]∙CHCl3 (2), [M2(L1)2], (3) and [M2(L2)2] (4), were characterized by elemental analysis, IR and NMR. Crystal structures of triphenylantimony(V) dicarboxylate complexes 1 and 2 were determined by single crystal X-ray diffraction. Structural analyses revealed that 1 and 2 adopt five-coordinated extremely distorted trigonal bipyramidal geometries, binding with three phenyl groups in the equatorial position and two deprotonated organic ligands (L) in the axial sites. The metal complexes, their metal salts and ligands were evaluated in vitro for their activities against Leishmania infantum and amazonensis promastigotes and Staphylococcus aureus and Pseudomonas aeruginosa bacteria. Both the metal complexes showed antileishmanial and antibacterial activities but the bismuth complexes were the most active. Intriguingly, complexation of organobismuth(V) salt reduced its activity against Leishmania, but increased it against bacteria. In vitro cytotoxic test of these complexes against murine macrophages showed that antimony(V) complexes were the least toxic. Considering the selectivity indexes, organoantimony(V) complexes emerge as the most promising antileishmanial agents and organobismuth(V) complex 3 as the best antibacterial agent.