Synthesis and Biological Evaluation of Benzo[b]thiophene Acylhydrazones as Antimicrobial Agents against Multidrug-Resistant Staphylococcus aureus

The benzo[b]thiophene nucleus and the acylhydrazone functional group were combined to prepare three new series of compounds for screening against Staphylococcus aureus. The reaction of substituted benzo[b]thiophene-2-carboxylic hydrazide and various aromatic or heteroaromatic aldehydes led to a collection of 26 final products with extensive structural diversification on the aromatic ring and on position 6 of the benzo[b]thiophene nucleus. The screening lead to the identification of eight hits, including (E)-6-chloro-N’-(pyridin-2-ylmethylene)benzo[b]thiophene-2-carbohydrazide (II.b), a non-cytotoxic derivative showing a minimal inhibitory concentration of 4 µg/mL on three S. aureus strains, among which were a reference classical strain and two clinically isolated strains resistant to methicillin and daptomycin, respectively.

Chemical composition, antioxidant, antimicrobial and antiviral activities of the leaf extracts of Syzygium myrtifolium

This study was conducted to evaluate the chemical composition and biological activities of the leaf extracts of Syzygium myrtifolium Walp. (Myrtaceae). The results indicate that the leaf extracts of S. myrtifolium contain various classes of phytochemicals (alkaloids, anthraquinones, flavonoids, phenolics, saponins, tannins and triterpenoids) and possess antioxidant, antibacterial, antifungal and antiviral activities. Ethyl acetate, ethanol, methanol, and water extracts exhibited significantly higher (p < 0.05) oxygen radical absorbance capacity and ferric-reducing antioxidant power than the hexane and chloroform extracts. However, all extracts exhibited stronger inhibitory activity against four tested species of yeasts (minimal inhibitory concentration: 0.02–0.31 mg mL–1) than against six tested species of bacteria (minimal inhibitory concentration: 0.16–1.25 mg mL–1). The ethanolic extract offered the highest protection of Vero cells (viability > 70 %) from the cytopathic effect caused by the Chikungunya virus while the ethyl acetate extract showed significant replication inhibitory activity against the virus (p < 0.001) using the replicon-enhanced green fluorescent protein reporter system.

The development of three ruthenium-based antimicrobial metallodrugs: Design, synthesis, and activity evaluation against Staphylococcus aureus

The development of new classes of antimicrobial is urgently needed due to the widespread occurrence of multi-resistant pathogens. In this study, three novel ruthenium complexes: [Ru(dmob)2(BTPIP)](PF6)2 (Ru(II)-1), [Ru(dbp)2(BTPIP)](PF6)2 (Ru(II)-2), and [Ru(dpa)2(BTPIP)](PF6)2 (Ru(II)-3) (dpa = 2,2’-dipyridylamine, dmob = 4,4’-dimethoxy-2,2’-bipyridyl, dbp = 4,4’-di- tert-butyl-2,2’-dipyridyl, BTPIP = 4-(benzo[ b]thiophen-2-yl)phenyl-1 H-imidazo[4,5- f][1,10]phenanthroline) are synthesized and investigated as antimicrobial metallodrugs. We demonstrate that all three complexes have significant antimicrobial activity against Staphylococcus aureus by testing their minimal inhibitory concentrations = 0.0015–0.0125 mg/mL. The antibacterial activity of the best active complex Ru(II)-3 is 13 times that of ofloxacin (minimal inhibitory concentration = 19.5 μg/mL). Importantly, Ru(II)-3 not only increases the susceptibility of Staphylococcus aureus to existing common antibiotics but also shows noticeably delayed and decreased resistance in Staphylococcus aureus since the minimal inhibitory concentration values of Ru(II)-3 only increased eightfold times after 20 passages. Furthermore, the biofilms formation and rabbit erythrocyte hemolysis assays verified that Ru(II)-3 also efficiently inhibit the biofilm formation and toxin secretion of Staphylococcus aureus.

Predicting the Outcome of Voriconazole Individualized Medication Using Integrated Pharmacokinetic/Pharmacodynamic Model

Therapeutic drug monitoring is considered to be an effective tool for the individualized use of voriconazole. However, drug concentration measurement alone doesn’t take into account the susceptibility of the infecting microorganisms to the drug. Linking pharmacodynamic data with the pharmacokinetic profile of individuals is expected to be an effective method to predict the probability of a certain therapeutic outcome. The objective of this study was to individualize voriconazole regimens by integrating individual pharmacokinetic parameters and pathogen susceptibility data through Monte Carlo simulations The individual pharmacokinetic parameters of 35 hospitalized patients who received voriconazole were calculated based on a validated population pharmacokinetic model. The area under the concentration-time curve for free drug/minimal inhibitory concentration (fAUCss/MIC) &gt; 25 was selected as the pharmacokinetic/pharmacodynamic (PK/PD) parameter predicting the efficacy of voriconazole. The cumulative fraction of response (CFR) of the target value was assessed. To verify this conclusion, a logistic regression analysis was used to explore the relationship between actual clinical efficiency and the CFR value. For the 35 patients, the area under the free drug concentration-time curve (fAUCss) was calculated to be 34.90 ± 21.67 mgh/L. According to the dualistic logistic regression analysis, the minimal inhibitory concentration (MIC) value of different kinds of fungi had a great influence on the effectiveness of clinical treatment. It also showed that the actual clinical efficacy and the CFR value of fAUCss/MIC had a high degree of consistency. The results suggest that it is feasible to individualize voriconazole dosing and predict clinical outcomes through the integration of data on pharmacokinetics and antifungal susceptibility.

Uji aktivitas antijamur ekstrak black garlic terhadap pertumbuhan jamur Candida albicans

Salah satu tanaman yang berfungsi sebagai antijamur adalah bawang putih yang diinovasikan menjadi produk bawang yang berwarna hitam atau black garlic. Penelitian ini bertujuan untuk mengetahui aktivitas antijamur ekstrak black barlic terhadap pertumbuhan jamur Candida albicans. Metoda dalam penelitian ini adalah bawang putih dipanaskan selama 35 hari pada suhu 65°C untuk mendapatkan black garlic. Black garlic diekstraksi dengan metode maserasi menggunakan pelarut methanol. Uji aktivitas antibakteri berdasarkan uji zona hambat, konsentrasi hambat minimal (KHM) dan konsentrasi bunuh minimal (KBM). Uji zona hambat dengan variasi konsentrasi ekstrak 100%, 90% dan 80%. Konsentrasi dengan nilai zona hambat yang baik akan dilanjutkan ke uji KHM dan KBM dengan pengenceran ke 1 sampai 5. Hasil penelitian menunjukkan bahwa zona hambat ekstrak Black Garlic dengan konsentrasi 100% memiliki zona hambat paling bagus yaitu 3,15 mm. Uji KHM optimum diperoleh pada pengenceran ke-5 dengan nilai OD terendah 0,460. Uji KBM dari ekstrak black garlic pada pengenceran ke-5 menunjukkan koloni jamur C. albicans masih tumbuh, sehingga dapat dikatakan bahwa ekstrak black garlic hanya mampu menghambat pertumbuhan jamur namun tidak bisa membunuh jamur C. albicans. Kata kunci: antijamur; black garlic; maserasi ABSTRACTActivity test of black garlic extract against the growth of the fungi Candida albicans. One plant that functions as an antifungal is garlic which is innovated into black garlic. The aim of this study is to indentify black garlic extract antifungal activity against of the Candida albicans. The method in this research was heated garlic for 35 days at temperature of 65°C. Black garlic was extracted by maceration method using methanol solvent. Antibacterial activity test based on inhibition zone test, minimal inhibitory concentration (MIC) and minimal kill concentration (MBC). Inhibition zone test with various extract concentrations of 100%, 90% and 80%. Concentrations with good inhibition zone values will be continued to the MIC and MBC tests with dilutions 1 to 5. The results showed that the inhibition zone of black garlic extract with a concentration of 100%, 3.15 mm. The optimum MIC test was obtained at the 5 dilution with the lowest OD value of absorbance 0.460. The MBC test of the black garlic extract at the 5 dilution showed C. albicans fungal colonies were still growing, so it can be said that the black garlic extract was only able to inhibit fungal growth but could not kill C. albicans fungi. Keywords: antifungal; black garlic; maceration

Effect of Hibiscus Sabdariffa Extract on Growth of Fusarium graminearum and the Expression of TRI4 and FG08079 Genes of the Fungus

Introduction: Fusarium graminearum produces trichothecenes, such as deoxynivalenol and secondary metabolite butenolide, which cause profound health problems in humans. In this research, the effect of acetone extract of Hibiscus sabdariffa is evaluated on growth of F. graminearum and expression of TRI4 and FG08079 genes, which are involved in deoxynivalenol and butenolide biosynthetic pathways, respectively. Methods: Minimal inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined. The expression of TRI4 and FG08079 genes were evaluated by teal-time PCR technique.Results: The MIC and MFC for acetone extract of Hibiscus sabdariffa against F. graminearum were 200 mg/mL and 400 mg/mL, respectively. Expression of TRI4 and FG08079 genes were significantly decreased by the acetone extract of red tea. Conclusion: The results showed that acetone extract of Hibiscus sabdariffa has inhibitory and fungicidal effects on F. graminearum and is effective in reducing the expression of TRI4 and FG08079 genes, which play important roles in deoxynivalenol and butenolide production.

Minimal Inhibitory Concentration and Minimal Bactericidal Concentration of Peppermint (Mentha piperita) extracts against standard microorganisms

Different plant extracts are considerably safe from infectious agents and may be used for medical purposes. The present research was conducted against the six standard microorganisms to quantify the antimicrobial activities of peppermint (Mentha piperita) extracts. The traditional approaches of minimum bactericidal concentration (MBC) and minimal inhibitory concentration (MIC) were used to approximate the antibacterial activities of ethanol, methanol, and chloroform peppermint extracts. The inhibitory function of the ethanol extract was comparable to that of chloroform (10 to 80mg/ml) and methanol (10 to 80mg/ml) against all gram-negative microorganisms. The minimum value of MIC was recorded for Streptococcus pyogenes (5mg/ml for extract of ethanol), followed by E. coli (10mg/ml for extract of ethanol) and then by Enterococcus faecalis (15mg/ml for extract of ethanol). With respect to the standard microorganisms, the MBC values were higher for both extracts than the corresponding MIC values. This work demonstrated the possible efficacy of antibacterial action on M. Piperita extracts from normal microorganisms (A. Baumenii, Escherichia coli, Streptococcus pyogenes, Enterococcus faecalis, Pseudomonas aeruginosa and Klebsiella pneumoniae), particularly ethanol extract. In summary, the peppermint ethanol extract had important growth-inhibiting effects on observed standard micro-organisms, followed by chloroform and methanol extracts. Further to in vitro and in vivo studies on a wide variety of natural microorganisms and therapeutic isolates are required to investigate and standardize the inhibitory activity of peppermint extracts against the most dangerous human pathogenic agents.

Prediction of Minimal Inhibitory Concentration of Meropenem Against Klebsiella pneumoniae Using Metagenomic Data

Minimal inhibitory concentration (MIC) is defined as the lowest concentration of an antimicrobial agent that can inhibit the visible growth of a particular microorganism after overnight incubation. Clinically, antibiotic doses for specific infections are determined according to the fraction of MIC. Therefore, credible assessment of MICs will provide a physician valuable information on the choice of therapeutic strategy. Early and precise usage of antibiotics is the key to an infection therapy. Compared with the traditional culture-based method, the approach of whole genome sequencing to identify MICs can shorten the experimental time, thereby improving clinical efficacy. Klebsiella pneumoniae is one of the most significant members of the genus Klebsiella in the Enterobacteriaceae family and also a common non-social pathogen. Meropenem is a broad-spectrum antibacterial agent of the carbapenem family, which can produce antibacterial effects of most Gram-positive and -negative bacteria. In this study, we used single-nucleotide polymorphism (SNP) information and nucleotide k-mers count based on metagenomic data to predict MICs of meropenem against K. pneumoniae. Then, features of 110 sequenced K. pneumoniae genome data were combined and modeled with XGBoost algorithm and deep neural network (DNN) algorithm to predict MICs. We first use the XGBoost classification model and the XGBoost regression model. After five runs, the average accuracy of the test set was calculated. The accuracy of using nucleotide k-mers to predict MICs of the XGBoost classification model and XGBoost regression model was 84.5 and 89.1%. The accuracy of SNP in predicting MIC was 80 and 81.8%, respectively. The results show that XGBoost regression is better than XGBoost classification in both nucleotide k-mers and SNPs to predict MICs. We further selected 40 nucleotide k-mers and 40 SNPs with the highest correlation with MIC values as features to retrain the XGBoost regression model and DNN regression model. After 100 and 1,000 runs, the results show that the accuracy of the two models was improved. The accuracy of the XGBoost regression model for k-mers, SNPs, and k-mers &amp; SNPs was 91.1, 85.2, and 91.3%, respectively. The accuracy of the DNN regression model was 91.9, 87.1, and 91.8%, respectively. Through external verification, some of the selected features were found to be related to drug resistance.