The Kirsten rat sarcoma viral G12C (KRAS^G12C) protein is one of the most common mutations in non-small-cell lung cancer (NSCLC). KRAS^G12C inhibitors are promising for NSCLC treatment, but their weaker activity in resistant tumors is their drawback. This study aims to identify new KRAS^G12C inhibitors from among the FDA-approved covalent drugs by taking advantage of artificial intelligence. The machine learning models were constructed using an extreme gradient boosting (XGBoost) algorithm. The models can predict KRAS^G12C inhibitors well, with an accuracy score of validation = 0.85 and Q²_Ext = 0.76. From 67 FDA-covalent drugs, afatinib, dacomitinib, acalabrutinib, neratinib, zanubrutinib, dutasteride, and finasteride were predicted to be active inhibitors. Afatinib obtained the highest predictive log-inhibitory concentration at 50% (pIC₅₀) value against KRAS^G12C protein close to the KRAS^G12C inhibitors. Only afatinib, neratinib, and zanubrutinib covalently bond at the active site like the KRAS^G12C inhibitors in the KRAS^G12C protein (PDB ID: 6OIM). Moreover, afatinib, neratinib, and zanubrutinib exhibited a distance deviation between the KRAS^G2C protein-ligand complex similar to the KRAS^G12C inhibitors. Therefore, afatinib, neratinib, and zanubrutinib could be used as drug candidates against the KRAS^G12C protein. This finding unfolds the benefit of artificial intelligence in drug repurposing against KRAS^G12C protein.

Mung bean (Vigna radiata L.) sprouts are increasingly consumed and have become part of a healthy diet. The sprouts are composed of proteins, carbohydrates, and biochemical compounds. During germination, the phytochemical compounds are significantly elevated, especially under stress conditions such as salinity, drought, extreme temperature, and illumination. The present study examined the effects of light and germination time on the bioactive compounds in mung bean sprout extracts. Mung bean seeds were sprouted under different light exposure conditions, and the phytochemical composition and antioxidant activity of sprout extracts were determined compared to seeds. The results show that tryptophan sharply decreased during germination. On the contrary, melatonin, polyphenols, and total phenolic content (TPC) were elevated with increased germination time, correlated with increased antioxidant activity. Sprouts germinated in the dark presented higher levels of melatonin and TPC compared with those germinated under 12 h light exposure (3.6- and 1.5-fold, respectively). In conclusion, germination can enhance valuable phytochemicals and antioxidant activity of mung bean sprouts. Mung bean sprouts may be a good alternative functional food for promoting human health.

Diabetes mellitus is a major predisposing factor for cardiovascular disease and mortality. α-Amylase and α-glucosidase enzymes are the rate-limiting steps for carbohydrate digestion. The inhibition of these two enzymes is clinically used for the treatment of diabetes mellitus. Here, in vitro study and machine learning models were employed for the chemical screening of inhibiting the activity of 31 plant samples on α-amylase and α-glucosidase enzymes. The results showed that the ethanolic twig extract of Pinus kesiya had the highest inhibitory activity against the α-amylase enzyme. The respective ethanolic extract of Croton oblongifolius stem, Parinari anamense twig, and Polyalthia evecta leaf showed high inhibitory activity against the α-glucosidase enzyme. The classification analysis revealed that the α-glucosidase inhibitory activity of Thai indigenous plants was more predictive based on phytochemical constituents, compared with the α-amylase inhibitory activity (1.00 versus 0.97 accuracy score). The correlation loading plot revealed that flavonoids and alkaloids contributed to the α-amylase inhibitory activity, while flavonoids, tannins, and reducing sugars contributed to the α-glucosidase inhibitory activity. In conclusion, the ethanolic extracts of P. kesiya, C. oblongifolius, P. anamense, and P. evecta have the potential for further chemical characterization and the development of anti-diabetic recipes.

The antioxidant activity of a traditional Thai formula has been studied and compared to each plant. The formula comprised the roots of Caesalpinia digyna Rottler, Huberantha cerasoides (Roxb.) Benth), Oxyceros horridus Lour, Antidesma ghaesembilla Gaerth, Combretum quadrangulare Kurz, and Ziziphus cambodiana Pierre. The stem was also studied in comparison. The ethanolic extract from each plant part and the mixed plants mimicking the traditional formula were prepared and investigated for antioxidant capability in vitro via DPPH radical scavenging and ferric-reducing antioxidant power assays. The phytochemical constituents were determined by chemical screening, total phenolic (TPC) and flavonoid contents (TFC), and high-performance liquid chromatography. The relationship between antioxidant activity and the contributed phytochemicals was determined using correlation analysis and principal component analysis (PCA). Results showed that extracts from both parts of the plant formula showed the highest antioxidant activity compared to a single plant extract. Among the six plants, C. digyna exhibited the highest TPC and antioxidant activity. TPC had a strong positive correlation with antioxidant activity. PCA revealed that gallic acid contributed to the antioxidant activity. In conclusion, the ethanolic extracts of the traditional formula and C. digyna have the potential for further chemical characterization and study related to antioxidant activity.

The intracellular uptake concentration determines drug absorption, drug activity, and toxicity. Sesamol, sesamin, and sesamolin are promising bioactive components from Sesame indicum L. Their respective intracellular uptake pathway and cytotoxicity were evaluated using melanoma and non-cancerous cells. Quantitative structure-activity relationship (QSAR) models were built to identify the molecular features affecting drug uptake in cells. The respective intracellular uptake pathway for sesamol vs. sesamin and sesamolin was carrier-mediated vs. passive transport. Topological polar surface area (PSA) and 2D autocorrections increase the intracellular concentration (C/M ratio) of these compounds. Sesamol has the lowest C/M ratio compared to sesamin and sesamolin, but only sesamol inhibits the cell viability of melanoma and provides an inhibition concentration at 50% (IC₅₀) against melanoma cells. The slightly aqueous solubility of sesamin and sesamolin, therefore, limits testing of their cytotoxicity. In conclusion, sesamol has the potential to inhibit melanoma cell growth, but requires improvement of the C/M ratio to increase its physicochemical properties. Thus, in order to investigate the cytotoxicity of sesamin and sesamolin against melanoma cells a solubility enhancer is needed.