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One of the main regulators in the cell cycle is cyclin-dependent kinase 4 and 6 (CDK4/6). FDA has approved CDK4/6 inhibitors for the treatment of patients with metastatic breast cancer. However, the development of selective agents remains problematic due to the conservation of their ATP binding sites. In the previous in silico study, ZINC585292724, ZINC585292587, ZINC585291674, and ZINC585291474 have been identified as potential inhibitors. Therefore, the present study aimed to analyze the selectivity and inhibitory activity of the four compounds against CDK4/6 in vitro as well as determine the potential for their further development in silico. The in vitro results showed that the four compounds had good selectivity towards both kinases, due to their similar structure. In agreement with the in silico results, ZINC585291674 produced the best inhibitory activity against CDK4 and CDK6, with IC50 of 184.14 nM and 111.78 nM, respectively. Their ADMET profile were also similar to reference compound of Palbociclib. Based on this, ZINC585291674 can be used as a lead compound for further inhibitor development. [ABSTRACT FROM AUTHOR]

Four derivatives of 2'‐hydoxychalcone were synthesized through Claisen‐Schmidt condensation by combining 2'‐hydroxyacetophenone and four different benzaldehyde derivatives (o‐vanillin, salicylaldehyde, p‐anisaldehyde, and benzaldehyde) in the presence of a base. The reactions took place in an ionic liquid, 1‐dodecyl‐3‐methylimidazolium bromide ([DDMIm]Br), and were facilitated by microwave irradiation. The reactions were completed within 10 to 15 minutes, yielding products with chemical yields ranging from 52.64 % to 83.42 %. The structures of the synthesized products were confirmed using 1H NMR and 13C NMR spectroscopy. Additionally, antimicrobial activity tests demonstrated the effectiveness of specific derivatives against Staphylococcus aureus and Escherichia coli, underscoring the importance of hydroxy and methoxy groups on the aromatic ring in inhibiting microbial growth. These findings provide valuable knowledge for developing chalcone derivatives with improved properties and potential applications in drug discovery. Furthermore, the synthesized products′ reactivity was analyzed using Frontier Molecular Orbital (FMO) and their reactivity site was mapped using Molecular Electrostatic Potential (MEP). Lastly, molecular docking analysis was attempted to explain antibacterial activities from all products. Nonetheless, the molecular docking simulations conducted in this study were inadequate to fully account for the antimicrobial activity observed in all the products. [ABSTRACT FROM AUTHOR]

Invasive fungal infections cause serious illness and death worldwide. Long-term therapeutic and preventative use of antifungal drugs in high-risk patients has caused resistance. Triazole antifungals are widely used to prevent and treat fungal infections, and therapeutic drug monitoring has been suggested to improve outcomes, reduce toxicity, and prevent drug resistance. Common methods used for monitoring triazole antifungal drugs in biological matrices such as blood, serum, and plasma include bioassay and instrumentation methods, especially liquid chromatography. Sample preparation is needed to remove interference from liquid chromatography for reliable results. This paper evaluates the use of liquid chromatography to analyze triazole antifungal agents. We provided various chromatographic techniques combined with different detector types to analyze triazole antifungal drugs in biological matrices. We also compared chromatography systems with different sample preparation methods in order to select the most suitable analytical method for bioanalysis. [ABSTRACT FROM AUTHOR]

Hepatitis is a liver illness caused by virus such as hepatitis A virus, hepatitis B virus and hepatitis C virus. Hepatitis B and C are considerably more usual and induce more cirrhosis and dead worldwide than hepatitis A. Although drugs that are currently often used in the medication of hepatitis B and C, the finding of recent drug from various resources including herbal has been intensively developed. Therefore, the purpose of this review is to consider the possibility of plant’s compounds as anti-HBV and anti-HCV. From the results of a review of several articles, several plant’s compound have shown effectiveness againts HBV and HCV by in silico, in vitro and in vivo studies. In conclusion, several plant’s active compounds are possibility to be developed as anti-hepatitis B and C. [ABSTRACT FROM AUTHOR]

Mycobacterium avium, one of the closest relatives of Mycobacterium tuberculosis (MTB), offers an advantage in studying MTB because of its tuberculosis-like effect in humans and host immune tolerance. This study examined the antimycobacterial action of ursolic acid and its regulation in macrophages during infection. Colonyforming units of the bacteria were determined in the cell lysate of macrophages and in the supernatant. The effect of ursolic acid on macrophages during infection was determined by analyzing the phosphorylation of the mitogen-activated protein kinase signaling pathway and the concentrations of tumor necrosis factor-a, interleukin-1ß, interleukin-6, and nitrite. The colony-forming units analysis demonstrated that ursolic acid reduced the presence of Mycobacterium avium both intracellularly (in macrophages) and extracellularly. It decreased the levels of tumor necrosis factor- a and interleukin-6 but increased the concentrations of interleukin-1ß and nitrite during infection. It also inhibited the phosphorylation of ERK1/2 but phosphorylated the C-Jun N-terminal kinase signaling pathway. The antimycobacterial effect of ursolic acid correlated with its ability to regulate the activation of macrophages. This dual ability made the ursolic acid-related elimination of the mycobacteria more effective. [ABSTRACT FROM AUTHOR]

Background: Green coffee beans are coffee beans of coffee fruit that have not yet been roasted. The use of green coffee beans as a weight-loss agent has been widely used worldwide, but nowadays there is a new way to enjoy coffee by adding kombucha culture to it, or what is known as kombucha coffee. The development of this fermented product preparation still requires a more in-depth study, one of which is related to the toxicity of the kombucha green coffee preparation. Objective: This research was aimed to determine LC50 values for robusta green coffee fermented with kombucha culture using zebrafish (Danio rerio) embryos using an in vivo method. Methods: This study observed the development of 20 zebrafish embryos administered one of five different concentrations of kombucha coffee preparation 24 hours up to 96 hours, with the experiment repeated three times. The percentage of embryo deaths was observed and analyzed using a probit model for LC50 concentration and analyzed using IBM SPSS Ver 23. Results: An LC50 for kombucha green coffee of 1294.29 ppm was obtained. Statistical tests on the concentration of kombucha coffee extracts were not significant differences with p-values > 0.05. Conclusion: The LC50 of robusta green coffee extract using zebrafish embryos of 1294.29 ppm included in the safe category. [ABSTRACT FROM AUTHOR]

In green synthesis of zinc oxide nanoparticles (ZnO NPs), the use of papaya extract as a capping and reducing agent shows promise for potential applications of these particles in biomedicine. However, toxicity evaluation is necessary to ensure the safety of humans and the environment. The zebrafish model is used to assess toxicity with embryo developmental observation as it is a rapid, simple method for screening of toxicity. The objective of the present study was to assess the toxicological characteristics of ZnO NPs produced from papaya extract using a zebrafish model. The preparation of plant extracts from papaya using two solvents (water and methanol) and characterization of bioactive compounds in the extracts were reported. ZnO NPs were synthesized from both plant extracts and characterized with scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. Toxicity evaluation was conducted on zebrafish embryos for 96 h. ZnO NPs synthesized from aqueous and methanol extracts had mean crystallite diameters of 13 and 12 nm, respectively. Mortality, hatching rate and malformation of zebrafish embryos were assessed at different concentrations of ZnO NPs. Both NPs showed high mortality rates at high concentrations, with 100 (aqueous) and 20 mg/l (methanol extract) being lethal for all embryos. Concentrations <10 mg/l for both synthesized ZnO NPs had similar results to the negative control, indicating a safe dosage for embryos. The hatching rate and malformation were also affected, with higher concentrations of NPs causing a delayed hatching rate and malformation in pericardial and yolk sac edema. Whole embryo mRNA expression of immune-associated genes, including IL-1 and -10 and TNF-α, was upregulated following lethal concentration 50 (LC50) ZnO NP exposure. ZnO NPs synthesized from papaya extract (both in aqueous and methanol environments) had a dose- and time-dependent embryonic toxicity effect. Hence, the present study demonstrated initial toxicity screening of ZnO NPs synthesized from plant extract. [ABSTRACT FROM AUTHOR]

The G1 phase of cell cycle progression is regulated by Cyclin-Dependent Kinase 4 (CDK4) as well as Cyclin-Dependent Kinase 6 (CDK6), and the acivities of these enzymes are regulated by the catalytic subunit, cyclin D. Cell cycle control through selective pharmacological inhibition of CDK4/6 has proven to be beneficial in the treatment of estrogen receptor-positive (ER-positive) breast cancer, particularly improving the progression-free survival of patients. Thus, targeting specific inhibition on CDK4/6 is bound to increase therapeutic efficiency. This study aimed to obtain CDK4/6 inhibitors through a pharmacophore-based virtual screening of the ZINC15 purchasable compound database using the in silico method. The pharmacophore model was designed based on the FDA-approved cdk4/6 inhibitor structures, and molecular docking was performed to further screen the hit compounds obtained. A total of eight compounds were selected based on docking results and interactions with CDK4 and CDK6, using palbociclib as the reference drug. According to the results, the compounds of ZINC585292724 and ZINC585291674 were the best compounds based on free binding energy, as well as hydrogen bond stability, and, therefore, exhibit potential as starting points in the development of CDK4/6 inhibitors. [ABSTRACT FROM AUTHOR]