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.

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.

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.