ABSTRACT
In this study, novel 4-(5-((2/3/4-substituted benzyl)thio)-4-(4-substituted phenyl)-4H-1,2,4-triazol-3-yl)-2-(pyridin-3/4-yl)thiazoles were synthesized following a multi-step synthetic procedure. All the compounds were screened with a panel of gram positive/negative bacteria, yeasts, and molds for antimicrobial activity using the disc diffusion method. Then, the minimum inhibitor concentration (MIC) and the minimum bactericidal concentration (MBC) values of active compounds were determined against Micrococcus luteus, Bacillus cereus, Listeria monocytogenes, and Staphylococcus aureus using the broth microdilution technique. These compounds were also screened for their inhibitory activities against S. aureus DNA gyrase by supercoiling assay. Furthermore, the crystal structure of S. aureus DNA gyrase B ATPase was subjected to a docking experiment to identify the possible interactions between the most active ligand and the active site. Lastly, the in silico technique was performed to analyze and predict the drug-likeness, molecular and ADME properties of the synthesized molecules.
Subject(s)
Anti-Infective Agents , DNA Gyrase , Anti-Bacterial Agents/chemistry , Anti-Infective Agents/pharmacology , DNA Gyrase/metabolism , Gram-Negative Bacteria , Gram-Positive Bacteria , Microbial Sensitivity Tests , Molecular Docking Simulation , Staphylococcus aureus , Structure-Activity Relationship , Thiazoles/chemistry , Thiazoles/pharmacologyABSTRACT
The importance of microbial natural compounds in drug research is increasing every year and they are used to prevent or treat a variety of diseases. Hypomyces chrysospermus is a cosmopolitan parasite of many Boletaceae members. Since not much work has been conducted to date, this study is undertaken to explore the anticancer effect, including the antiproliferative and antimetastatic activity of Hypomyces chrysospermus. The aim of this study is to determine the antiproliferative and antimetastatic activity of Hypomyces chrysospermus ethyl acetate extract, having antioxidant activity, against A549, Caco2, MCF-7 human cancer and CCD-19 Lu and CCD 841 CoN healthy human cell lines. Firstly, cytotoxic activity was determined by the WST-1 assay. After cell proliferations and anti-metastatic effects were investigated by a real-time cell analysis system (RTCA-DP) and IC50 concentrations were calculated for each cell line. In addition, the expression levels of Apaf-1, TNF and NF-kB mRNA in cancer cells were investigated with RealTime-PCR. The ethyl acetate extract of Hypomyces chrysospermus presented anticancer activities including antiproliferative and antimetastatic effects. Hypomyces chrysospermus as a source of biologically active metabolites can be used as an important resource in the development of new anticancer effective agents.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Hypocreales/metabolism , A549 Cells/drug effects , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Apoptotic Protease-Activating Factor 1/metabolism , Basidiomycota/pathogenicity , Caco-2 Cells/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Humans , Hypocreales/physiology , MCF-7 Cells/drug effects , NF-kappa B/metabolism , Plant Extracts/pharmacology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
In this study, the culture requirements of the Cerrena unicolor OBCC 5005 strain were determined to optimize bioactive exopolysaccharide production in submerged culture. The effects of initial medium pH, carbon and nitrogen sources, inoculum age and amount, and mineral source on exopolysaccharide and mycelial biomass production by the C. unicolor OBCC 5005 strain were studied using a one-factor-at-a-time method. The highest exopolysaccharide production was obtained when culture parameters were used as initial medium pH: 5.5, 5% sucrose, 5% mycological peptone, and 5% of 4-day inoculants in the presence of 5 mM Fe2+. Optimized culture conditions at a flask scale were applied to a 3-L stirred tank reactor. As a result, 7.92 g/L and 7.34 g/L maximum exopolysaccharide production in optimized conditions at flask and stirred-tank reactor scales were achieved, respectively. The present study is the first to prove that C. unicolor can yield high bioactive exopolysaccharide production at flask and stirred-tank reactor scales.
