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.

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.

Corynebacterium pseudotuberculosis (Cp) is a pathogenic bacterium that causes caseous lymphadenitis (CLA), ulcerative lymphangitis, mastitis, and edematous to a broad spectrum of hosts, including ruminants, thereby threatening economic and dairy industries worldwide. Currently there is no effective drug or vaccine available against Cp. To identify new targets, we adopted a novel integrative strategy, which began with the prediction of the modelome (tridimensional protein structures for the proteome of an organism, generated through comparative modeling) for 15 previously sequenced C. pseudotuberculosis strains. This pan-modelomics approach identified a set of 331 conserved proteins having 95-100% intra-species sequence similarity. Next, we combined subtractive proteomics and modelomics to reveal a set of 10 Cp proteins, which may be essential for the bacteria. Of these, 4 proteins (tcsR, mtrA, nrdI, and ispH) were essential and non-host homologs (considering man, horse, cow and sheep as hosts) and satisfied all criteria of being putative targets. Additionally, we subjected these 4 proteins to virtual screening of a drug-like compound library. In all cases, molecules predicted to form favorable interactions and which showed high complementarity to the target were found among the top ranking compounds. The remaining 6 essential proteins (adk, gapA, glyA, fumC, gnd, and aspA) have homologs in the host proteomes. Their active site cavities were compared to the respective cavities in host proteins. We propose that some of these proteins can be selectively targeted using structure-based drug design approaches (SBDD). Our results facilitate the selection of C. pseudotuberculosis putative proteins for developing broad-spectrum novel drugs and vaccines. A few of the targets identified here have been validated in other microorganisms, suggesting that our modelome strategy is effective and can also be applicable to other pathogens.

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 &...