The transcriptional regulator (TcaR) enzyme plays an important role in biofilm formation. Prevention of TcaR-DNA complex formation leads to inhibit the biofilm formation is likely to reveal therapeutic ways for the treatment of bacterial infections. To identify the novel ligands for TcaR and to provide a new idea for drug design, two efficient drug design methods, such as pharmacophore modeling and structure-based drug design, were used for virtual screening of database and lead optimization, respectively. Gemifloxacin (FDA-approved drug) was considered to generate the pharmacophore model for virtual screening of the ZINC database, and five hits, namely ZINC77906236, ZINC09550296, ZINC77906466, ZINC09751390, and ZINC01269201, were identified as novel inhibitors of TcaR with better binding energies. Using structure-based drug design, a set of 7a–7p inhibitors of S. epidermidis were considered, and Mol34 was identified with good binding energy and high fitness score with improved pharmacological properties. The active site residues ARG110, ASN20, HIS42, ASN45, ALA38, VAL63, VAL68, ALA24, VAL43, ILE57, and ARG71 are playing a promising role in inhibition process. In addition, we performed DFT simulations of final hits to understand the electronic properties and their significant role in driving the inhibitor to adopt apposite bioactive conformations in the active site. Conclusively, the newly identified and designed hits from both the methods are promising inhibitors of TcaR, which can hinder biofilm formation.

This study was designed to investigate the protective effect of a methanol extract of Chungkookjang (CKJ) on high glucose induced oxidative stress in LLC-PK 1 cells (renal tubular epithelial cells), which are susceptible to oxidative stress. Freeze dried CKJ powder was extracted with methanol, and the extract solution was concentrated, and then used in this study. To determine the protective effect of CKJ extract, oxidative stress was induced by exposing of LLC-PK 1 cells to high glucose (30 mM) or normal glucose (5 mM) for 24 hr. Exposure of LLC-PK 1 cells to high glucose for 24 hr resulted in a significant (p<0.05) decrease in cell viability, catalase, SOD and GSH-px activity and a significant (p<0.05) increase in intracellular ROS level and thiobarbituric acid reactive substances (TBARS) formation in comparison to the cells treated with 5 mM glucose. CKJ extract treatment decreased intracellular ROS level and TBARS formation, and increased cell viability and activities of antioxidant enzymes including catalase, SOD and GSH-px in high glucose pretreated LLC-PK 1 cells. These results suggest that CKJ extract may be able to protect LLC-PK 1 cells from high glucose-induced oxidative stress, partially through the antioxidative defense systems.

To further the goal of isolating Bacillus sp. from commercial chungkukjang (CKJ) for a development of a probiotic dietary adjunct using soymilk or milk, antioxidant activity of CKJ purchased from the Sunchang Traditional Village in Chunbook province was examined. Six CKJ samples were evaluated and 3 were selected based on the results of the physicochemical analysis and sensory evaluation for further antioxidant study. IC 50 for DPPH scavenging activity of methanol extracts of CKJ ranged from 238.1 to 345.7 μg/mL. CKJ exhibited over 80% scavenging of •OH and ONOO-at concentrations of 100 μg/mL and 250 μg/mL, respectively. O 2 -and NO scavenging activities of three CKJ were increased in a dose dependent manner with the concentration tested from 100 to 1000 μg/mL. In this study, the methanol extract of CKJ exhibited a great reduction capability and powerful free radical scavenging activity, especially against OH -and ONOO -, which are the most toxic radicals responsible for oxidative damage in the body. However, radical scavenging effects of CKJ on DPPH, O 2 -, and nitrite radical were rather moderate. In conclusion, CKJ may reduce the oxidative stress in the body by scavenging the free radicals.

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