Ellagic acid controls cell proliferation and induces apoptosis in breast cancer cells via inhibition of cyclin-dependent kinase 6

Cyclin-Dependent Kinase 6 (CDK6) plays an important role in cancer progression, and thus, it is considered as an attractive drug target in anticancer therapeutics. This study presents an evaluation of dietary phytochemicals, capsaicin, tocopherol, rosmarinic acid, ursolic acid, ellagic acid (EA), limonene, caffeic acid, and ferulic acid for their potential to inhibit the activity of CDK6. Molecular docking and fluorescence binding studies revealed appreciable binding affinities of these compounds to the CDK6. Among them, EA shows the highest binding affinity for CDK6, and thus a molecular dynamics simulation study of 200 ns was performed to get deeper insights into the binding mechanism and stability of the CDK6-EA comple

Antibacterial Functionalization and Simultaneous Coloration of Wool Fiber with the Application of Plant-Based Dyes

High susceptibility of wool toward bacterial growth owing to proteinous nature and moisture retention ability leads to need for antibacterial functionalization of wool to cure the resulting deterioration. Antibacterial colored wool was designed via application of Terminalia chebula, Alkanna tinctoria, and Tagetes erecta natural dyes. Characteristics in terms of color and antibacterial activity were compared to correlate coloring compound’s effect on characteristics of dyes and, both T. chebula and A. tinctoria dyes inferred themselves actively resisting bacterial growth while T. erecta was not efficient against bacterial strains. Colorful shades of good color and fastness properties were obtained from selected natural dyes on woolen yarn. Results show Bacillus subtilis and Staphylococcus aureus (gram positive) were highly resisted by the effect of T. chebula and A. tinctoria dyes, and T. chebula among them proved best in terms of both color characteristics and antibacterial potential

Antimicrobial and fluorescence finishing of woolen yarn with Terminalia arjuna natural dye as an ecofriendly substitute to synthetic antibacterial agents

The current study deals with the use of Terminalia arjuna natural dye as an ecofriendly finishing agent for producing highly functional antimicrobial and fluorescent woolen yarn along with the evaluation of kinetic and thermodynamic adsorption characteristics. The effect of pH on the adsorption was investigated, showing an increase in adsorption capacity with decreasing pH over the range of 2–9, with maximum adsorption at pH 3.5. Two kinetic equations pseudo-first order and pseudo-second order were employed for determining adsorption rates. The pseudo-second order equation provided the best fit to experimental data with an activation energy of 105.58 kJ mol−1, indicating chemisorption. The equilibrium adsorption data was fitted to Langmuir, Freundlich and Redlich–Peterson adsorption isotherms. The adsorption behavior accorded with the Redlich–Peterson isotherm with exceptionally high regression coefficients for dyeing temperatures of 50, 70 and 90 °C with dye concentration varying from 0.5–10% (o.w.f). Comparative results of the colorimetric properties (CIEL*a*b* and K/S) using a spectrophotometer under D65 illuminant (10° standard observer) and color fastness (light, wash, and rub) of dyed woolen yarns were studied to quantify the effect of metal mordants. The antimicrobial potential of Terminalia arjuna solution and dyed woolen yarn were assessed in terms of percentage inhibition of bacterial growth against a wide variety of bacterial strains, showing more than 85% inhibition. Reduction in antimicrobial activity of dyed woolen yarn was observed with mordanted samples, however they were found to retain more antimicrobial activity as compared to unmordanted samples as a function of successive washing cycles. The chemical nature of different mordants and wool–mordant–dye complex forming ability were found to have significant impact on the colorimetric and fluorescence characteristics of dyed woolen yarn

Ellagic Acid Controls Cell Proliferation and Induces Apoptosis in Breast Cancer Cells via Inhibition of Cyclin-Dependent Kinase 6

Cyclin-Dependent Kinase 6 (CDK6) plays an important role in cancer progression, and thus, it is considered as an attractive drug target in anticancer therapeutics. This study presents an evaluation of dietary phytochemicals, capsaicin, tocopherol, rosmarinic acid, ursolic acid, ellagic acid (EA), limonene, caffeic acid, and ferulic acid for their potential to inhibit the activity of CDK6. Molecular docking and fluorescence binding studies revealed appreciable binding affinities of these compounds to the CDK6. Among them, EA shows the highest binding affinity for CDK6, and thus a molecular dynamics simulation study of 200 ns was performed to get deeper insights into the binding mechanism and stability of the CDK6-EA complex. Fluorescence binding studies revealed that EA binds to the CDK6 with a binding constant of K = 107 M−1 and subsequently inhibits its enzyme activity with an IC50 value of 3.053 µM. Analysis of thermodynamic parameters of CDK6-EA complex formation suggested a hydrophobic interaction driven process. The treatment of EA decreases the colonization of cancer cells and induces apoptosis. Moreover, the expression of CDK6 has been downregulated in EA-treated human breast cancer cell lines. In conclusion, this study establishes EA as a potent CDK6 inhibitor that can be further evaluated in CDK6 directed anticancer therapies

Insights into the Antibacterial Activity of Prolactin-Inducible Protein against the Standard and Environmental MDR Bacterial Strains

Background: Prolactin inducible protein (PIP) is a small secretary glycoprotein present in most biological fluids and contributes to various cellular functions, including cell growth, fertility, antitumor, and antifungal activities. Objectives: The present study evaluated the antibacterial activities of recombinant PIP against multiple broad-spectrum MDR bacterial strains. Methods: The PIP gene was cloned, expressed and purified using affinity chromatography. Disk diffusion, broth microdilution, and growth kinetic assays were used to determine the antibacterial activities of PIP. Results: Disk diffusion assay showed that PIP has a minimum and maximum zone of inhibition against E. coli and P. aeruginosa, respectively, compared to the reference drug ampicillin. Furthermore, growth kinetics studies also suggested that PIP significantly inhibited the growth of E. coli and P. aeruginosa. The minimum inhibitory concentration of PIP was 32 µg/mL for E. coli (443), a standard bacterial strain, and 64 µg/mL for Bacillus sp. (LG1), an environmental multidrug-resistant (MDR) strain. The synergistic studies of PIP with ampicillin showed better efficacies towards selected bacterial strains having MDR properties. Conclusion: Our findings suggest that PIP has a broad range of antibacterial activities with important implications in alleviating MDR problems

Design, Synthesis and Mechanistic Studies of Novel Isatin-Pyrazole Hydrazone Conjugates as Selective and Potent Bacterial MetAP Inhibitors

Methionine aminopeptidases (MetAPs) are attractive drug targets due to their essential role in eukaryotes as well as prokaryotic cells. In this study, biochemical assays were performed on newly synthesized Isatin-pyrazole hydrazones (PS1–14) to identify potent and selective bacterial MetAPs inhibitors. Compound PS9 inhibited prokaryotic MetAPs, i.e., MtMetAP1c, EfMetAP1a and SpMetAP1a with Ki values of 0.31, 6.93 and 0.37 µM, respectively. Interestingly, PS9 inhibited the human analogue HsMetAP1b with Ki (631.7 µM) about ten thousand-fold higher than the bacterial MetAPs. The in vitro screening against Gram-positive (Enterococcus faecalis, Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa, Klebsiella pneumonia and Escherichia coli) bacterial strains also exhibited their antibacterial potential supported by minimum bactericidal concentration (MBC), disk diffusion assay, growth curve and time-kill curve experiments. Additionally, PS6 and PS9 had synergistic effects when combined with ampicillin (AMP) and ciprofloxacin (CIP) against selective bacterial strains. PS9 showed no significant cytotoxic effect on human RBCs, HEK293 cells and Galleria mellonella larvae in vivo. PS9 inhibited the growth of multidrug-resistant environmental isolates as it showed the MIC lower than the standard drugs used against selective bacterial strains. Overall, the study suggested PS9 could be a useful candidate for the development of antibacterial alternatives

Development of Oxadiazole-Sulfonamide-Based Compounds as Potential Antibacterial Agents

In this work, substituted 1,2,4-oxadiazoles (OX1− OX27) were screened against five bacterial strains, identified to be OX7 and OX11 as growth inhibitors with minimum inhibitory concentration (MIC) values of 31.25 and 15.75 μg/mL, respectively. The growth inhibitory property of OX7 and OX11 was further validated by disk diffusion, growth curve, and time kill curve assays. Both disrupted biofilm formation with 92−100% reduction examined by the XTT assay were further visualized by scanning electron microscopy analysis. These compounds in combination with ciprofloxacin also exhibit synergy against Escherichia coli cells. With insignificant cytotoxic behavior on HEK293 cells, human red blood cells, and Galleria mellonella larvae, OX11 was tested against 28 multidrug resistant environmental isolates of bacteria and showed inhibition of Kluyvera georgiana and Citrobacter werkmanii strains with 32 and 16 μg/mL MIC values, respectively. The synergistic behavior of OX11 with ampicillin showed many fold reductions in MIC values against K. georgiana and Klebsiella pneumoniae multidrug resistant strains. Further, transmission electron microscopy analysis of OX11-treated E. coli cells showed a significantly damaged cell wall, which resulted in the loss of integrity and cytosolic oozing. OX11 showed significant changes in the secondary structure of human serum albumin (HSA) in the presence of OX11, enhancing HSA stability. Overall, the study provided a suitable core for further synthetic alterations and development as an antibacterial agen