Novel thiazolinyl-picolinamide-based palladium(II) complex extenuates the virulence and biofilms of vulvovaginal candidiasis (VVC) causing Candida.

Candida infections are growing all over the world as a result of their resistance to anti-fungal drugs. This raises concerns about public health, particularly in cases of vulvovaginal candidiasis (VVC). Therefore, the need for effective treatment options for Candida infections has become crucial. The main goal of the study is to evaluate the efficacy of novel palladium metal complexes against fluconazole-resistant Candida spp., particularly C. albicans and C. auris. The process begins with identifying the minimum inhibitory concentration (MIC), followed by growth curve assays, colony morphology analysis, characterization, and gene expression analysis. The investigation revealed that sub-MIC of Pd(II) complex B (250 µg/mL) inhibited Candida spp. more effectively than amphotericin B (500 µg/mL). Further, Pd(II) complex B drastically reduced the growth of Candida spp. biofilms by 70-80% for nascent biofilms and 70-75% for mature biofilms. Additionally, the yeast-to-hyphal switch and SEM studies revealed that Pd(II) complex B effectively hinders the growth of drug-resistant Candida cells. The gene expression investigation also evidenced that Pd(II) complex B downregulated virulence genes in C. albicans (ERG, EFG, UME6, and HGC) and C. auris (ERG, CDR, and HGC). The findings showed that Pd(II) complex B effectively inhibited the growth of Candida biofilm formation and was reported as a potential anti-biofilm agent against Candida spp. that are resistant to drugs.

Palladium(II) Metal Complex Fabricated Titanium Implant Mitigates Dual-Species Biofilms in Artificial Synovial Fluid.

Metallodrugs have a potent application in various medical fields. In the current study, we used a novel Palladium(II) thiazolinyl picolinamide complex that was directly fabricated over the titanium implant to examine its potency in inhibiting dual-species biofilms and exopolysaccharides. Additionally, inhibition of mono- and dual-species biofilms by coated titanium plates in an in vitro joint microcosm was performed. The study was carried out for 7 days by cultivating mono- and dual-species biofilms on titanium plates placed in both growth media and artificial synovial fluid (ASF). By qPCR analysis, the interaction of co-cultured biofilms in ASF and the alteration in gene expression of co-cultured biofilms were studied. Remarkable alleviation of biofilm accumulation and EPS secretion was observed on the coated titanium plates. The effective impairment of biofilms and EPS matrix of biofilms on Pd(II)-E-coated titanium plates were visualized by Scanning Electron Microscopy. Moreover, coated titanium plates improved the adhesion of osteoblast cells, which is crucial for a bone biomaterial. The potential bioactivity of coated plates was also confirmed at the molecular level using qPCR analysis. The stability of coated plates in ASF for 7 days was examined with FESEM-EDAX analysis. Collectively, the present study provided an excellent anti-infective effect on Pd(II)-E-coated titanium plates without affecting their biocompatibility with bone cells.

Investigation on the Anticancer and Antibacterial Mechanism of Thiazoline/Imidazoline Derived Palladium(II) Complexes.

Biological activities of a series of palladium(II) complexes (M1-M9) bearing N∩ N, N∩ S, and N∩ O chelating ligands are reported. The palladium complexes were tested for their cytotoxic properties against human cervical cancer (HeLa) cells and antibacterial activity against Gm+ve and Gm-ve bacteria. Among the palladium complexes studied (M1-M9), the complex M5, M8, and M9 were found to be more effective in inhibiting the proliferation of HeLa cells. Hence, these complexes were further investigated for their potential role in cellular damage and apoptosis. DCFDA staining, Rhodamine 123 staining and DNA cleavage assay revealed that complex M5, M8 and M9 induced apoptotic cell death in HeLa cells through ROS generation, DNA damage and mitochondrial depolarization. Computational and titration studies also indicated strong electrostatic interaction with DNA groove. Most of the complexes exhibited good antibacterial activity against both Gm+ve and Gm-ve bacteria. The antibacterial activity of the compounds could not be correlated with their anticancer activity indicating a differential mechanism at their effective concentrations. The detailed study on the antibacterial mechanism of the most potent complex M7 revealed that it exerted its antibacterial activity by inhibiting the function of FtsZ and perturbing the localization of the Z-ring at the mid cell.

Effect of palladium(II) complexes on NorA efflux pump inhibition and resensitization of fluoroquinolone-resistant Staphylococcus aureus: in vitro and in silico approach.

Staphylococcus aureus leads to diverse infections, and their treatment relies on the use of antibiotics. Nevertheless, the rise of antibiotic resistance poses an escalating challenge and various mechanisms contribute to antibiotic resistance, including modifications to drug targets, enzymatic deactivation of drugs, and increased efflux of antibiotics. Hence, the quest for innovative antimicrobial solutions has intensified in the face of escalating antibiotic resistance and the looming threat of superbugs. The NorA protein of S. aureus, classified as an efflux pump within the major facilitator superfamily, when overexpressed, extrudes various substances, including fluoroquinolones (such as ciprofloxacin) and quaternary ammonium. Addressing this, the unexplored realm of inorganic and organometallic compounds in medicinal chemistry holds promise. Notably, the study focused on investigating two different series of palladium-based metal complexes consisting of QSL_PA and QSL_PB ligands to identify a potent NorA efflux pump inhibitor that can restore the susceptibility to fluoroquinolone antibiotics. QSL_Pd5A was identified as a potent efflux pump inhibitor from the real-time efflux assay. QSL_Pd5A also resensitized SA1199B to ciprofloxacin at a low concentration of 0.125 µg/mL without elucidating cytotoxicity on the NRK-62E cell line. The in vitro findings were substantiated by docking results, indicating favorable interactions between QSL_Pd5A and the NorA efflux pump.

Transition metal complex laminated bioactive implant alleviates Methicillin Resistant Staphylococcus aureus virulence.

Orthopedic implant infections cause a serious threat after implantation. The major source of implant infection is biofilms which are highly tolerant to antibiotics due to the presence of rigid biofilm matrix. Hence to overcome biofilm mediated implant infections, we developed a novel antibiofilm agent, palladium (II) thiazolinyl picolinamide complex (Pd(II)-E). From our study, it was found that Pd(II)-E have profound biofilm inhibition activity and also reduced various virulence factors of Methicillin resistant Staphylococcus aureus (MRSA) including slime synthesis, Phenol soluble modulin (PSM) mediated spreading, Exopolysaccharides production and staphyloxanthin synthesis. Further, Pd(II)-E was coated over the titanium plates which was confirmed using EDX (Energy Dispersive X-Ray) analysis. The Pd(II)-E coated plates were able to prevent the biofilm formation on them which was evident under a Scanning electron microscope (SEM) and several virulent genes were found to be downregulated in the biofilms on the coated titanium plates which confirmed by qPCR. From our findings, it was found that Pd(II)-E coated titanium implants would be an effective alternate approach for preventing biofilm mediated implant infections.

Heteroleptic pincer palladium(II) complex coated orthopedic implants impede the AbaI/AbaR quorum sensing system and biofilm development by Acinetobacter baumannii.

Implant-associated infections mediated by Acinetobacter baumannii biofilms have become a major concern in the healthcare sector. As biofilm formation by this important pathogen is mediated by quorum sensing, quorum sensing inhibitors (QSI) have gained much attention. The present study confirms that novel thiazolinyl-picolinamide based palladium(II) complexes had good biofilm disruptive and QSI properties against A. baumannii. Key QS-mediated virulence factors like pili mediated surface motility and polysaccharide production were inhibited by the best Pd(II) complex (E). This also showed potent inhibitory activity against both the standard and clinical strains of A. baumannii. Molecular docking analysis also proved the potent binding affinity of Pd(II)-E with the virulence targets. The Pd(II) complex also disrupted preformed biofilms and down-regulated the expression of QS mediated virulence genes in the biofilms established on implant material (titanium plates). As a whole, the present study showed that the novel thiazolinyl-picolinamide based Pd(II) complexes offer a promising anti-infective strategy to combat biofilm-mediated implant infections.

Spectral Characterization of Purpurin Dye and Its Application in pH Sensing, Cell Imaging and Apoptosis Detection.

Purpurin (1,2,4-trihydroxy-9,10-anthraquinone) is a natural red dye obtained from the red madder plant that is widely used in food and dyeing industries. The present study investigated the characteristics of purpurin and its application as a pH-sensitive probe to detect the pH of solutions and intracellular pH of mammalian and bacterial cells. Purpurin exhibited high pH-sensitive behavior, low analytes interference, high stability with pKa of 4.6 and visible colorimetric change. 1H NMR and FTIR studies indicated protonation of phenolic hydroxyl group under acidic condition with hypsochromic shift in the absorption and fluorescence spectra relative to that of basic condition. Cell culture studies using HeLa cells revealed that purpurin is well tolerated by the cells and the fluorescent imaging result indicated excellent cell permeability with possible use of the dye to detect the pH fluctuations in living cells under various physiological conditions such as apoptosis. Microbiological studies indicated that the dye could be used for visualization of bacteria under acidic condition.

Quaternization and oxidation reactions of cyclodiphosphazane derivatives and their copper(I) and gold(I) complexes.

The reactions of cyclodiphosphazane derivatives cis-{(t)BuN(H)P(µ-N(t)Bu)2PN(H)(t)Bu} (1), cis-{MeN(C4H8N)P(µ-N(t)Bu)2P(NC4H8Me)} (2) and {(Me2NCH2CH2O)P(µ-N(t)Bu)2P(OCH2CH2NMe2)} (3) with methyl iodide and methyl triflate and their subsequent reactions with elemental sulfur and selenium are reported. Interestingly, the reactions of 1-3 with an excess of methyl iodide resulted in quaternising only one phosphorus atom in cis-[{(t)BuNHP(µ-N(t)Bu)2P(CH3)NH(t)Bu}](I) (4), two exocyclic nitrogen atoms and one of the phosphorus atoms in cis-{(Me2NC4H8N)P(µ-N(t)Bu)2P(CH3)(NC4H8NMe2)}](I)3 (7) and only two exocyclic nitrogen atoms in cis-[{(Me3NCH2CH2O)P(µ-N(t)Bu)2P(OCH2CH2NMe3)}](I)2 (8). The reaction of 1 with one equiv. of methyl triflate produced cis-[{(t)BuN(H)P(µ-N(t)Bu)2P(CH3)N(H)(t)Bu}]OTf (5), whereas the same reaction in a 1 : 2 molar ratio afforded cis-{(t)BuN(H)P(CH3)(µ-N(t)Bu)2P(CH3)N(H)(t)Bu}(OTf)2 (6). Compounds 4 and 5 showed poor solubility in water, whereas 7 and 8 were high melting crystalline solids with moderate to good water solubility. Treatment of 4 with either elemental sulfur or selenium gave both cis- and trans-chalcogenide derivatives. Similar reactions of 7 and 8 produced both mono- and bischalcogenides. Reactions between 4 or 7 and CuI yielded dinuclear complexes, cis-[{Cu2(µ-I)3((t)BuN(H)P)(µ-N(t)Bu)2(P(CH3)N(H)(t)Bu)]2}(I)] (15) and cis-[{Cu2(µ-I)3[(Me2NC4H8N)P(µ-N(t)Bu)2P(CH3)(NC4H8NMe2)]2}(I)5] (16), while the reaction of 8 with CuI produced a coordination polymer [{Cu2(µ-I)3(µ-N(t)BuP)2(OCH2CH2NMe3)2}I]∞ (17), containing triiodo-bridged [Cu2(µ-I)3] linkers. The molecular structures of several of these compounds were confirmed by single crystal X-ray diffraction studies. The Cu(I)···Cu(I) distance of 2.55 Å in 15 is quite short and is the same as that found in copper metal and also in complexes containing [Cu2(µ-I)3] linkers. All the metal complexes exhibit strong intra-, inter- or both intra- and inter-molecular hydrogen bonding interactions.

Two crystalline modifications of 1,1'-thiobis(2-naphthol).

The title compound, C(20)H(14)O(2)S, has been obtained in two monoclinic forms, which differ in their unit-cell dimensions, compactness of packing and conformation. Pairwise association of molecules occurs via complementary O-H...O hydrogen bonding.