Jin-Hwan Kwak

In Vitro and In Vivo Antibacterial Activities of DW-224a, a New Fluoronaphthyridone

ABSTRACT DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.

In Vitro and In Vivo Activities of LCB01-0371, a New Oxazolidinone

ABSTRACT LCB01-0371 is a new oxazolidinone with cyclic amidrazone. In vitro activity of LCB01-0371 against 624 clinical isolates was evaluated and compared with those of linezolid, vancomycin, and other antibiotics. LCB01-0371 showed good activity against Gram-positive pathogens. In vivo activity of LCB01-0371 against systemic infections in mice was also evaluated. LCB01-0371 was more active than linezolid against these systemic infections. LCB01-0371 showed bacteriostatic activity against Staphylococcus aureus.

Chemical Composition and Antimicrobial Activity of the Essential Oil of Apricot Seed

In traditional oriental medicine, apricot (Prunus armeniaca L.) seed has been used to treat skin diseases such as furuncle, acne vulgaris and dandruff, as well as coughing, asthma and constipation. This study describes the phytochemical profile and antimicrobial potential of the essential oil obtained from apricot seeds (Armeniacae Semen). The essential oil isolated by hydrodistillation was analysed by gas chromatography–mass spectroscopy. Benzaldehyde (90.6%), mandelonitrile (5.2%) and benzoic acid (4.1%) were identified. Disc diffusion, agar dilution and gaseous contact methods were performed to determine the antimicrobial activity against 16 bacteria and two yeast species. The minimum inhibitory concentrations ranged from 250 to 4000, 500 to 2000 and 250 to 1000 µg/mL for Gram‐positive bacteria, Gram‐negative bacteria and yeast strains, respectively. The minimum inhibitory doses by gaseous contact ranged from 12.5 to 50, 12.5 to 50 and 3.13 to 12.5 mg/L air for Gram‐positive bacteria, Gram‐negative bacteria and yeast strains, respectively. The essential oil exhibited a variable degree of antimicrobial activity against a range of bacteria and yeasts tested. Copyright

Synthesis and antimicrobial activity of imidazole and pyridine appended cholestane-based conjugates.

A series of 3α-amino-5α-cholestane and 3α,7α-diamino-5α-cholestane derivatives containing imidazole and pyridine rings were synthesized by simple and effective reductive amination, and their in vitro activities against a range of Gram-positive and Gram-negative strains were evaluated. Most of the compound exhibited enhanced activity against MRSA pathogen. 3α,7α-Di(pyridylmethyl)amino-5α-cholestane 10 showed the highest potency in these series toward the Gram-positive bacteria, Staphylococcus epidermidis 887E, with the lowest MIC value of 1 μg/mL.

A concise synthesis and antimicrobial activities of 3-polyamino-23,24-bisnorcholanes as steroid-polyamine conjugates.

A series of steroid-polyamine conjugates were synthesized and evaluated for their antimicrobial activity. This study was focused on the effect of stereochemistry at the C-3 and C-5 of steroids and types of polyamine at C-3 on activity against various human pathogens. All the conjugates exhibited strong antimicrobial activities against Gram-positive strains. Compound 18 was found to be the most potent in these series with a MIC value as low as 1 μg/mL against the bacterium Staphylococcus aureus ATCC6538P.

Antibacterial activity of LCB01-0062, a novel oxazolidinone

LCB01-0062, a novel oxazolidinone, has potent antibacterial activity against clinical isolates of Gram-positive bacteria. The in vitro activity of LCB01-0062 was compared with that of linezolid, oxacillin, erythromycin, ciprofloxacin, vancomycin and quinupristin/dalfopristin. Among the tested agents, LCB01-0062 showed the most potent antibacterial activity against meticillin-resistant Staphylococcus aureus, meticillin-resistant coagulase-negative staphylococci and vancomycin-resistant enterococci. LCB01-0062 was 4-8-fold more active than linezolid, the first oxazolidinone drug, against Gram-positive bacteria. The time-kill curves of LCB01-0062 were analysed at concentrations of 0.5×, 1×, 2×, 4× and 8× the minimum inhibitory concentration against S. aureus strains. LCB01-0062 showed bacteriostatic activity during 24 h. LCB01-0062 was also more effective than linezolid against S. aureus in a systemic mouse model of infection.

In Vitro Activities of LCB 01-0648, a Novel Oxazolidinone, against Gram-Positive Bacteria

Oxazolidinones are a novel class of synthetic antibacterial agents that inhibit bacterial protein synthesis. Here, we synthesized and tested a series of oxazolidinone compounds containing cyclic amidrazone. Among these compounds, we further investigated the antibacterial activities of LCB01-0648 against drug-susceptible or resistant Gram-positive cocci in comparison with those of six reference compounds. LCB01-0648 showed the most potent antimicrobial activities against clinically isolated Gram-positive bacteria. Against the methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCNS) isolates, LCB01-0648 showed the lowest MIC90s (0.5 mg/L) among the tested compounds. In addition, LCB01-0648 had the lowest minimum inhibitory concentrations (MICs) against the four linezolid-resistant S. aureus (LRSA) strains (range 2–4 mg/L). The results of the time–kill studies demonstrated that LCB01-0648 at a concentration 8× the (MIC) showed bactericidal activity against methicillin-susceptible Staphylococcus aureus MSSA or MRSA, but showed a bacteriostatic effect against LRSA. These results indicate that LCB01-0648 could be a good antibacterial candidate against multidrug-resistant (MDR) Gram-positive cocci.

Antimicrobial Activity of Zabofloxacin against Clinically Isolated Streptococcus pneumoniae

Zabofloxacin is a novel fluoroquinolone agent that has potent activity against gram-positive pathogens. In this study, we confirmed that zabofloxacin showed the most potent in vitro and in vivo activities against drug-resistant Streptococcus pneumoniae. Among the fluoroquinolone compounds, zabofloxacin showed the most potent in vitro activity against clinical isolates of penicillin-sensitive S. pneumoniae (minimum inhibitory concentration, MIC90: 0.03 mg/L) and penicillin-resistant S. pneumoniae (MIC90: 0.03 mg/L). Against quinolone-resistant S. pneumoniae, zabofloxacin (MIC90: 1 mg/L) was more active than ciprofloxacin, sparfloxacin, and moxifloxacin; however, its activity was the same as that of gemifloxacin. The in vivo activity of zabofloxacin was most potent among the quinolone compounds tested against the systemic infection and respiratory tract infection models in mice.

N-cholesteryl amino acid conjugates and their antimicrobial activities

A series of N-cholesteryl amino acid conjugates have been synthesized using a reductive amination protocol in good yield and purity. All the synthesized conjugates were evaluated for their in vitro antimicrobial activities against Gram positive and Gram negative bacteria. Among the conjugates tested, N-cholesteryl GABA 12 showed the highest potency toward the methicillin-resistant Staphylococcus aureus with the lowest MIC value of 2 μg/mL. Hemolytic activities of the compounds 3, 4, 11, and 12 were determined. All compounds tested had no significant hemolytic activity up to >50 μg/mL.

Mon1 Is Essential for Fungal Virulence and Stress Survival in Cryptococcus neoformans

Abstract Mon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab GTPase and is essential for vacuole trafficking and autophagy in eukaryotic organisms. Here, we identified and characterized the function of Mon1, an ortholog of Saccharomyces cerevisiae Mon1, in a human fungal pathogen, Cryptococcus neoformans. Mutation in mon1 resulted in hypersensitivity to thermal stress. The mon1 deletion mutant exhibited increased sensitivity to cell wall and endoplasmic reticulum stress. However, the mon1 deletion mutant showed more resistance to the antifungal agent fluconazole. In vivo studies demonstrated that compared to the wild-type strain, the mon1 deletion mutant attenuated virulence in the Galleria mellonella insect model. Moreover, the mon1 deletion mutant was avirulent in the murine inhalation model. These results demonstrate that Mon1 plays a crucial role in stress survival and pathogenicity in C. neoformans.