Structure-Activity Relationship Study and Design Strategies of Hydantoin, Thiazolidinedione, and Rhodanine-Based Kinase Inhibitors: A Two-Decade Review.

Cancer is one of the most prominent causes of the rapidly growing mortality numbers worldwide. Cancer originates from normal cells that have acquired the capability to alter their molecular, biochemical, and cellular traits. The alteration of cell signaling enzymes, such as kinases, can initiate and amplify cancer progression. As a curative method, the targeted therapy utilized small molecules' capability to inhibit kinase's cellular function. This review provides a brief history (1999-2023) of Small Molecule Kinase Inhibitors (SMKIs) discovery with their molecular perspective. Furthermore, this current review also addresses the application and the development of hydantoin, thiazolidinedione, and rhodanine-based derivatives as kinase inhibitors toward several subclasses (EGFR, PI3K, VEGFR, Pim, c-Met, CDK, IGFR, and ERK) accompanied by their structure-activity relationship study and their molecular interactions. The present work summarizes and compiles all the important structural information essential for developing hydantoin, thiazolidinedione, and rhodanine-based kinase inhibitors to improve their potency in the future.

Two new flavonols from Macaranga inermis pax & K.Hoffm.

Four isoprenylated flavonols, including two new compounds, macainermisins A-B (1-2), and two known compounds, sinoflavonoid P (3), broussoflavonol F (4), were isolated from the leaves of Macaranga inermis. A combination of HRESIMS, UV, 1D, and 2D NMR spectra elucidated the structures of 1-2. Flavonols (1-4) were evaluated against three cancer cells. Compound 1 showed high cytotoxicity against WiDR with an IC50 value of 0.93 µM, and compound 2 was active towards HeLa and WiDR (IC50 values of 0.90 and 0.94 µM), and compound 3 showed high activity towards 4T1 and HeLa (IC50 values of 0.83 and 0.98 µM).

Recent advances of carbonyl olefination via McMurry coupling reaction.

McMurry coupling reaction utilizes the low-valent titanium reagents and carbonyl compounds to produce olefins. The wide synthetic application of McMurry reagents in intermolecular and intramolecular coupling reactions, tandem coupling reactions, and keto ester coupling reactions of carbonyl compounds for the last five years have been reviewed. The resulting coupling reaction produces natural and non-natural products, including strained olefins and unusual molecules as a candidate for nanomaterials, pharmaceuticals, electronic materials, and so forth. The advantages, scope, and limitations along with the improvement of the McMurry coupling reaction, including the addition of high functional group compatibility, McMurry reagents substitution, and several other treatments, have also been discussed.

Synergetic effect of the surface ligand and SiO2 driven photoluminescence stabilization of the CH3NH3PbBr3 perovskite magic-sized clusters.

Zero-dimensional Perovskite Magic-size Clusters play crucial roles in understanding and controlling nucleation and growth of semiconductor nanoparticles. However, their metastability behavior is a critical hindrance for reliable characterizations. Here, we report the first demonstration of using an excess amount of surface ligand and SiO2 as novel passivation for synthesizing the magic-sized clusters (MSCs) by the Ligand-assisted reprecipitation method. A synergetic effect between an excessed surface ligand and SiO2 inhibits the protonation and deprotonation reaction between amine-based and acid-based ligand, leading to enhanced PL stability. The obtained CH3NH3PbBr3 PMSCs/SiO2 retain 70% of its initial emission intensity in ambient conditions for 20 days. This passivation approach opens an entirely new avenue for the reliable characterizations of CH3NH3PbBr3 PMSCs, which will significantly broaden their application for understanding and controlling nucleation and growth of semiconductor nanoparticles.

Metabolite profiles and antidiabetic activity of the green beans of Luwak (civet) coffees.

Metabolite profiles of green beans (the caged and the wild) Luwak (civet) coffees were evaluated by NMR techniques combined with chemometrics. The bioactivities of the green coffee beans were examined with antioxidant tests and an alpha-glucosidase inhibitory assay. Both are invitro tests related to the antidiabetic properties. Our results showed the civet coffees possessed unique metabolomes and were different from the regular arabica coffee. Both civet coffees were characterized by higher concentrations of alanine, citrate, lactate, malate, and trigonelline. Lactate and lipids were found as the most important compounds discriminating the caged civet coffee from the wild civet coffee. Bioactivity assays exhibited the antidiabetic activities of the civet coffees were better than the activity of the regular coffee. These results suggested that the civet coffees are promising functional foods reducing the diabetes risk. It is the first report evaluating metabolite profiles of both civet coffees using 1H NMR-based metabolomics.

Calotetrapterins A-C, three new pyranoxanthones and their cytotoxicity from the stem bark of Calophyllum tetrapterum Miq.

Three new pyranoxanthones, calotetrapterins A-C (1-3) were isolated from the stem bark of Calophyllum tetrapterum Miq along with three known xanthones, α-mangostin (4), garciniafuran (5), and pyranojacareubin (6). All structures were elucidated based on their IR, UV, HRESIMS, 1 D (1H, 13C) and 2 D (HMBC, HMQC) NMR spectral data. Compounds 1-6 were tested to P-388 cells for cytotoxic activity, compound 2 exhibited high activity with IC50 value 1.0 µM.

Antibacterial and Antifungal Activity of Three Monosaccharide Monomyristate Derivatives.

Microbial infections remains a serious challenge in food industries due to their resistance to some of the well-known antibacterial and antifungal agents. In this work, a novel monomyristoyl ester (fructosyl monomyristate) and two other derivatives (i.e., glucosyl and galactosyl monomyristates) were successfully synthesized from myristic acid and monosaccharides in two-step reactions. First, the myristic acid was converted to myristoyl chloride, and then the myristoyl chloride was reacted with fructose, glucose and galactose separately to produce the corresponding monosaccharide monomyristate derivatives. The structures of the synthesized products were confirmed by Fourier transform infrared (FTIR), proton and carbon nuclear magnetic resonance (1H- and 13C-NMR), and mass spectral (MS) data. The monomyristates esters were obtained in reaction yields of 45.80%-79.49%. The esters were then evaluated for their antimicrobial activity using the disc diffusion test. It was found that the esters exhibited a medium antibacterial activity against gram-positive bacteria; however, they showed a weak antibacterial activity against gram-negative bacteria. Amongst the esters, galactosyl myristate yielded the highest antibacterial activity against Salmonella typhimurium, Staphylococcus aureus and Bacillus subtilis, while glucosyl monomyristate exhibited the highest antibacterial activity only against Escherichia coli. Additionally, all products showed remarkable antifungal activity against Candida albicans. These findings demonstrate that monosaccharide monomyristate derivatives are promising for use as biocompatible antimicrobial agents in the future.

Anti-angiogenic effect of α-mangostin.

Eleven known prenyl xanthones, isolated from the pericarp of Garcinia mangostana, were tested for their ability to inhibit the phosphorylation of kinase domain receptor (KDR) tyrosine kinase. α-Mangostin was found to inhibit phosphorylation of KDR. α-Mangostin also showed to inhibit phosphorylation of the Y1175 residue of KDR (10 µM). This is the first report that α-mangostin inhibited the phosphorylation of KDR tyrosine kinase and also the Y1175 residue of KDR. α-Mangostin also showed inhibitory effects on proliferation of human umbilical vein endothelial cells (HUVECs) (IC(50) 1.2 µM) and human umbilical artery endothelial cells (IC(50) 2.4 µM), as well as the migration (IC(50) 0.034 µM) and tubule formation (at the concentrations of 0.6 and 1.2 µM) of HUVECs. These results suggest that the inhibition of the phosphorylation of KDR tyrosine kinase is concerned in the anti-angiogenic activity of α-mangostin.

Oil productivity of the tropical marine diatom Thalassiosira sp.

To understand the potential of cultivating tropical marine diatom Thalassiosira sp. to produce biofuel, biodiesel product properties and growth characteristics of Thalassiosira sp. in three different media were investigated. After medium evaluation, significant Thalassiosira sp. cell growth was observed in both Walne and enriched seawater media, but not in plain seawater medium. The microalgae grew well in alkaline condition (pH range of 8.0-8.8). The average biomass density cultured in Walne and enriched seawater media on the 6th day was 4.36 and 2.50 g L(-1), respectively. Based on ESI-IT-MS spectra, the TAGs of algal oil were identified as POP, POO, and SOO, and the FAMEs as oleic acid methyl ester. The oil productivity of Thalassiosira sp. cultured in Walne and enriched seawater media were 150 and 290 µL L(-1) d(-1), respectively. The density and kinematic viscosity of Thalassiosira sp. biodiesel were 0.857 g mL(-1) and 1.151 mm(2) s(-1).

Artoindonesianins N and O, new prenylated stilbene and prenylated arylbenzofuran derivatives from Artocarpus gomezianus.

A new prenylated stilbene, named artoindonesianin N (1) and a new prenylated arylbenzofuran, named artoindonesianin O (2), were isolated from Artocarpus gomezianus Wall. ex Trec. (Moraceae). Their structures were elucidated as 1 and 2 on the basis of spectroscopic evidence. Along with these new compounds, a known phenolic compound was also isolated from this plant and identified as oxyresveratrol (3).