Qingguo Meng

Synthesis, molecular docking, and biological evaluation of novel triazole derivatives as antifungal agents.

Twenty‐eight novel triazole derivatives (compounds 1a‐v, 2a‐f) have been synthesized for structure–activity relationship studies as antifungal agents. The compounds were designed on the basis of the structure of fluconazole and molecular modeling of the active site of the cytochrome P450 14α‐demethylase (CYP51). All of them are reported for the first time. Their chemical structures are characterized by 1H NMR, 13C NMR, LC‐MS, and elemental analysis. The antifungal activities have been evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 1a‐v exhibited higher activity against nearly all fungi tested except Aspergillus fumigatus (A. fum) than fluconazole (FCZ). The computational molecular docking experiments indicated that the inhibition of CYP51 involves a coordination bond with iron of the heme group, a hydrophilic H‐bonding region, a hydrophobic region, and a narrow hydrophobic binding cleft.

Novel 3-substituted ocotillol-type triterpenoid derivatives as antibacterial candidates.

Plant‐derived triterpenoid saponins are involved in the plant defense system by targeting bacterial membranes. A series of ocotillol‐type triterpenoid derivatives were synthesized starting from PPD, one of the main components of Panax ginseng and their antibacterial activity against several representative bacteria were evaluated. Compounds 5 and 11 exhibited excellent antibacterial activity with MIC values of 1 μg/mL against Staphylococcus aureus and 8 μg/mL and 4 μg/mL against Bacillus subtilis, respectively. Furthermore, when compounds 5 and 11 were combined with two commercial antibiotics kanamycin and chloramphenicol, they showed strong synergistic activity at sub‐MIC levels against S. aureus USA300 and B. subtilis 168. Moreover, chloramphenicol turned from a bacteriostatic to a bactericidal agent when combined with compound 11 against B. subtilis 168.

Synthesis and Antibacterial Evaluation of Novel 3-Substituted Ocotillol-Type Derivatives as Leads

Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In this paper, a series of antibacterial ocotillol-type C-24 epimers modified from natural 20(S)-protopanaxadiol were synthesized and evaluated for their antibacterial activity. According to the screening results of Gram-positive bacteria (B. subtilis 168 and MRSA USA300) and Gram-negative bacteria (P. aer PAO1 and A. baum ATCC19606) in vitro, the derivatives exhibited good antibacterial activity, particularly against Gram-positive bacteria with an minimum inhibitory concentrations (MIC) value of 2–16 µg/mL. The subsequent synergistic antibacterial assay showed that derivatives 5c and 6c enhanced the susceptibility of B. subtilis 168 and MRSA USA300 to chloramphenicol (CHL) and kanamycin (KAN) (FICI < 0.5). Our data showed that ocotillol-type derivatives with long-chain amino acid substituents at C-3 were good leads against antibiotic-resistant pathogens MRSA USA300, which could improve the ability of KAN and CHL to exhibit antibacterial activity at much lower concentrations with reduced toxicity.

Hmga2 Expression in Renal Carcinoma and its Clinical Significance / Ekspresija Hmga2 U Karcinomu Bubrega I Njen Klinički Značaj

Summary Background: The objective of this study is to detect HMGA2 expression in renal carcinoma to explore its relationship with clinicopathology and its significance in prognosis. Expressions of HMGA2 mRNA and protein were detected in 50 renal carcinoma specimens, 50 corresponding adjacent normal kidney tissue samples and 40 renal benign tumour specimens via reverse transcription polymerase chain reaction and immunohistochemical assay. Methods: Expression analysis was performed along with clinical data analysis. The relative expression levels of HMGA2 mRNA in renal carcinoma, renal benign tumour tissues and adjacent normal renal tissues were 0.84±0.23, 0.19±0.06 and 0.08±0.04, respectively. HMGA2 protein positive rates were 68.0%, 7.5% and 2.0%, with a significant difference (P<0.05). HMGA2 expression was not significantly correlated with gender, age, tumour size and histological type (P>0.05), but was significantly correlated with TNM stages and lymph node metastasis (P<0.05). Conclusions: The expressions of HMGA2 gene and protein in renal carcinoma were closely correlated with tumour formation, progression and metastasis. HMGA2 may become a powerful new pathological marker and prognostic factor for renal carcinoma. Kratak sadr žaj Uvod: Cilj studije je da se otkrije ekspresija HMGA2 u karcinomu bubrega kako bi se istražio njen odnos sa kliničkom patologijom kao i značaj u prognozi. Metode: Ekspresije mDNK i proteina HMGA2 određene su u 50 uzoraka karcinoma bubrega, 50 odgovarajućih uzoraka okolnog normalnog tkiva bubrega i 40 uzoraka benignih tumora bubrega putem reverzne transkripcije - lančane reakcije polimeraze i imunohistohemijskim testovima. Analiza ekspresije obavljena je zajedno sa analizom kliničkih podataka. Rezultoti: Relativni nivoi ekspresije mDNK HMGA2 u karci- nomu bubrega, tkivima benignih bubrežnih tumora i tkivima okolnog normalnog bubrežnog tkiva bili su redom: 0,84±0,23, 0,19±0,06 i 0,08±0,04. Pozitivne stope proteina HMGA2 bile su 68,0%, 7,5% i 2,0%, uz postojanje znacajne razlike (P<0,05). Ekspresija HMGA2 nije značajno korelisala sa polom, starošću, veličinom tumora i histološkim tipom (P>0,05), ali je bila u značajnoj korelaciji sa stupnje- vima TNM i metastazama limfnih čvorova (P<0,05). Zaključak: Ekspresije gena i proteina HMGA2 u karcinomu bubrega bile su u bliskoj korelaciji sa formiranjem, progresijom i metastazama tumora. HMGA2 bi mogao da postane moćan novi patološki marker i prognostički faktor za karcinom bubrega

Design, synthesis and biological evaluation of azithromycin glycosyl derivatives as potential antibacterial agents.

A series of 11,12-cyclic carbonate azithromycin-4″-O-carbamoyl glycosyl derivatives were designed, synthesized, and evaluated as antibacterial agents to search for target compounds with excellent activity. The results of preliminary antibacterial tests against eight strains in vitro revealed that all of the title compounds exhibited improved activities with broad spectrum compared with the parent compound. The glycosylated side chains may be the pharmacophores responsible for the improved activity.

Synthesis and Antibacterial Evaluation of a Series of 11,12-Cyclic Carbonate Azithromycin-3-O-descladinosyl-3-O-carbamoyl Glycosyl Derivatives

A novel series of 11,12-cyclic carbonate azithromycin-3-O-descladinosyl-3-O-carbamoyl glycosyl derivatives were designed, synthesized, and evaluated for their antibacterial activities in vitro. Most of these compounds had significant antibacterial activity against seven kinds of susceptible strains. In particular, compound G1 exhibited the most potent activity against methicillin-resistant Streptococcus pneumoniae 943 (MIC: 1 μg/mL), Staphylococcus pneumoniae 746 (MIC: 2 μg/mL), Streptococcus pyogenes 447 (MIC: 8 μg/mL), and Escherichia coli 236 (MIC: 32 μg/mL), which were two-, four-, four-, four-, and eight-fold stronger activity than azithromycin, respectively. Additionally, compound G2 exhibited improved activity against methicillin-resistant Staphylococcus aureus MRSA-1 (MIC: 8 μg/mL), Streptococcus pneumoniae 943 (MIC: 2 μg/mL), Staphylococcus pneumoniae 746 (MIC: 2 μg/mL), and Escherichia coli 236 (MIC: 32 μg/mL), which were two-, two-, four-, and eight-fold better activity than azithromycin, respectively. As for methicillin-resistant Staphylococcus aureus MRSA-1, compound G6 presented the most excellent activity (MIC: 4 μg/mL), showing four-fold higher activity than azithromycin (MIC: 16 μg/mL) and erythromycin (MIC: 16 μg/mL). However, compared with other compounds, compounds G7 and G8 with the disaccharide side chain were observed the lower activity against seven strains.