Evaluation of antimicrobial, anticancer potential and Flippase induced leakage in model membrane of Centella asiatica fabricated MgONPs.

The use of chemically synthesized nanoparticles and crude plant extracts as antimicrobial -anticancer agents have many limitations. In this study, we have used Centella asiatica extract (CaE) having relatively less explored but tremendous medicinal properties, as reducing and stabilizing agents to green synthesize magnesium oxide nanoparticles (MgONPs) using magnesium nitrate. In comparison to the bulk material, capabilities of Ca-MgONPs as an improved antibacterial, antifungal, and anticancer agent in human prostatic carcinoma cells (PC3), as well as membranolytic capability in model cell membrane, were studied. The phyto-functionalized Ca-MgONPs were characterized using UV-Visible spectroscopy (UV-Vis), Transmission Electron Microscopy (TEM), Energy Dispersive X-Ray Spectroscopy (EDX), X-ray Diffraction (XRD), Fourier Transform Infra-Red Spectroscopy (FT-IR) and Atomic Force Microscopy (AFM). Observation of characteristic peaks by spectroscopic and microscopic analysis confirmed the synthesis of Ca-MgONPs. The Ca-MgONPs showed broad spectrum of bactericidal activity against both gram-positive and gram-negative bacteria and fungicidal activity against two species of the Candida fungus. The Ca-MgONPs also exhibited dose-dependent and selective inhibition of proliferating PC3 cells with IC50 of 123.65 ± 4.82 µg/mL at 24 h, however, without having any cytotoxicity toward non-cancerous HEK293 cells. Further studies aimed at understanding the probable mechanism of toxicity of Ca-MgONPs in PC3 cells, the results indicated a significant reduction in cell migration capacities, increment in cytosolic ROS, loss of mitochondrial transmembrane potential, DNA damage and S-phase cell cycle arrest. Ca-MgONPs also induced pore formation in a synthetic large unilamellar vesicle. Thus, Ca-MgONPs might be useful in the effective management of several human pathogens of concern and some more cancer types.

Untargeted Metabolomics in Piper betle Leaf Extracts to Discriminate the Cultivars of Coastal Odisha, India.

Betel leaf is consumed as a mouth freshener due to its characteristic flavor, aromaticity, and medicinal values. Abundance of phytochemicals in betel leaf contributes towards unique qualitative features. Screening of metabolites is quintessential for identifying flavoring betel leaves and their origin. Metabolomics presently lays emphasis on the cumulative application of gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopic approaches. Here we adopted different protocols based on the above-mentioned analytical metabolomics platform for untargeted plant metabolite profiling followed by multivariate analysis methods and a phytochemical characterization of Piper betel leaf cultivars endemic to coastal Odisha, India. Based on variation in the solvent composition, concentration of solvent, extraction temperature, and incubation periods, five extraction methods were followed in GC-MS and NMR spectroscopy of betel leaf extracts. Phytochemical similarities and differences among the species were characterized through multivariate analysis approaches. Principal component analysis, based on the relative abundance of phytochemicals, indicated that the betel cultivars could be grouped into three groups. Our results of FTIR-, GC-MS-, and NMR-based profiling combined with multivariate analyses suggest that untargeted metabolomics can play a crucial role in documenting metabolic signatures of endemic betel leaf varieties.

C-lysine conjugates: pH-controlled light-activated reagents for efficient double-stranded DNA cleavage with implications for cancer therapy.

Double-stranded DNA cleavage of light-activated lysine conjugates is strongly enhanced at the slightly acidic pH (<7) suitable for selective targeting of cancer cells. This enhancement stems from the presence of two amino groups of different basicities. The first amino group plays an auxiliary role by enhancing solubility and affinity to DNA, whereas the second amino group, which is positioned next to the light-activated DNA cleaver, undergoes protonation at the desired pH threshold. This protonation results in two synergetic effects which account for the increased DNA-cleaving ability at the lower pH. First, lysine conjugates show tighter binding to DNA at the lower pH, which is consistent with the anticipated higher degree of interaction between two positively charged ammonium groups with the negatively charged phosphate backbone of DNA. Second, the unproductive pathway which quenches the excited state of the photocleaver through intramolecular electron transfer is eliminated once the donor amino group next to the chromophore is protonated. Experiments in the presence of traps for diffusing radicals show that reactive oxygen species do not contribute significantly to the mechanism of DNA cleavage at the lower pH, which is indicative of tighter binding to DNA under these conditions. This feature is valuable not only because many solid tumors are hypoxic but also because cleavage which does not depend on diffusing species is more localized and efficient. Sequence-selectivity experiments suggest combination of PET and base alkylation as the chemical basis for the observed DNA damage. The utility of these molecules for phototherapy of cancer is confirmed by the drastic increase in toxicity of five conjugates against cancer cell lines upon photoactivation.