Emerging cephalosporins

Several cephalosporins are in clinical development as broad-spectrum agents with potent activity against multi-resistant staphylococci as well as the Gram-positive and Gram-negative bacteria normally susceptible to advanced generation cephalsoporins. These agents represent a novel activity for the class and challenge a dogma that β-lactams do not have clinically useful activity against multi-resistant staphylococci. The most advanced of these agents, ceftobiprole, is approaching registration and, if approved, will present physicians with a new paradigm in treatment of serious infections by multi-resistant organisms.     

抗MRSA天然产物的研究进展

目的综述国内外抗MRSA（耐甲氧西林金黄色葡萄球菌）天然产物的研究进展。方法查阅关于抗MRSA天然产物的国内外文献。结果共计报道抗MRSA天然产物约85个,其中58个来源于微生物,26个来源于植物,另外1个来源于海洋动物海绵;主要包括环肽类、生物碱类、萜类、醌类、黄酮类和大环内酯类等结构类型,其中11个化合物含有氯、溴或硫元素;30个化合物体外抗MRSA的MIC〈5μg.mL-1。结论微生物和植物的次级代谢产物中含有结构特异、活性显著的抗MRSA成分,随着临床上耐药病原菌不断地被分离发现和防治MRSA感染形势的日趋严峻,有必要对微生物和植物的抗MRSA成分展开广泛而又深入的研究。     

Evaluating the ototoxicity of an anti-MRSA peptide KR-12-a2

Introduction

Methicillin-resistant staphylococcus aureus is an emerging problem for the treatment of chronic suppurative otitis media, and also for pediatric tympanostomy tube otorrhea. To date, there are no effective topical antibiotic drugs to treat methicillin-resistant staphylococcus aureus otorrhea.

Two new isoflavanones from Erythrina costaricensis

Two new isoflavanones, 5,3′-dihydroxy-4′-methoxy-5′-(3-methyl-1,3-butadienyl)-2″,2″-dimethylpyrano[5,6:6,7]isoflavanone (1) and 5,3′-dihydroxy-5′-(3-hydroxy-3-methyl-1-butenyl)-4′-methoxy-2″,2″-dimethylpyrano[5,6:6,7]isoflavanone (2), together with two known isoflavonoids, cristacarpin, and euchrenone b₁₀, were isolated from the stems of Erythrina costaricensis. Their structures were established on the basis of spectroscopic evidence. These new compounds are rare isoflavanones, possessing both a 2,2-dimethylpyran substituent and a prenyl analog. The antibacterial activities of 1 and 2 against the methicillin-resistant Staphylococcus aureus were examined.     

迷迭香中鼠尾草酸的抗MRSA活性研究

目的对迷迭香中鼠尾草酸的抗MRSA(耐甲氧西林金黄色葡萄球菌)活性进行研究。方法采用硅胶柱层析法对迷迭香提取物(鼠尾草酸含量72.4%)进行分离精制获得鼠尾草酸,然后以标准菌株MRSA ATCC 33592和临床分离菌株MRSA 01~08为指示菌,采用微量肉汤稀释法测定鼠尾草酸对MRSA菌株的最低抑菌浓度和最低杀菌浓度;运用棋盘格法设计试验,采用微量肉汤稀释法,分别测定鼠尾草酸与苯唑西林钠或氨苄西林钠的联合抗MRSA作用。结果分离精制获得含量为98.6%的鼠尾草酸,其对指示菌MRSAATCC33592和MRSA 01~08的最低抑菌浓度的范围为8~16μg.mL 1,最低杀菌浓度均为32μg.mL 1;与苯唑西林钠或氨苄西林钠合用对MRSA指示菌的部分抑菌浓度指数(FICIs):0.5≤FICIs<1.0。结论鼠尾草酸具有明显的抗MRSA活性,与苯唑西林钠或氨苄西林钠合用时呈现抗MRSA的相加或协同作用。     

Three new diphenyl ether derivatives from the fermentation products of an endophytic fungus Phomopsis fukushii

Three new diphenyl ethers (1-3), together with four known isopentylated diphenyl ethers derivatives (4-7), were isolated from the fermentation products of an endophytic fungus Phomopsis fukushii. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1-3 were evaluated for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. The results revealed that compounds 1 and 2 showed strong inhibitions with inhibition zone diameters (IZD) of 20.2 ± 2.5 mm and 17.9 ± 2.2 mm, respectively. Compound 3 also showed good inhibition with IZD 15.2 ± 1.8 mm. The IZD data of compound 1 is close to that of positive control with IZD 21.9 ± 2.1 mm.     

A new drimane sesquiterpenoid glycoside from the seeds of Antiaris toxicaria

A new drimane sesquiterpenoid glycoside, named 7-drimen-3β,11-diol 3-O-β-d-glucopyranoside, was isolated from the 95% EtOH extract of the seeds of Antiaris toxicaria (Pers.) Lesch. The chemical structure was completely elucidated using a combination of 1D and 2D NMR techniques (COSY, HMQC, HMBC, and ROESY) and HR-ESI-MS analysis. The compound showed inhibitory activities toward methicillin-resistant Staphylococcus aureus (MRSA), chronic myelogenous leukemia (K562), and human hepatoma (SMMC-7721) cell lines.     

Inhibition of methicillin-resistant Staphylococcus aureus (MRSA) by antimicrobial peptides (AMPs) and plant essential oils

Context: Drug-resistant bacterial infections cause considerable patient mortality and morbidity. The annual frequency of deaths from methicillin-resistant Staphylococcus aureus (MRSA) has surpassed those caused by human immunodeficiency virus/acquired immune deficiency syndrome. The antimicrobial peptides (AMPs), plant essential oils (EOs) and their combinations have proven to be quite effective in killing a wide selection of bacterial pathogens including MRSA.

Objectives: This review summarizes the studies in the use of AMPs, plant EOs and their combinations for coping with MRSA bacteria, and to formulate new prospects for future studies on this topic.

Methods: The sources of scientific literature such as PubMed, library search, Google Scholar, Science Direct and electronic databases such as ‘The Antimicrobial Peptide Database’, ‘Collection of Anti-Microbial Peptides’ and ‘YADAMP’. Physicochemical data of anti-MRSA peptides were determined by Scientific DataBase Maker software.

Results: Of the 118 peptides, 88 exhibited an activity against MRSA with the highest activity of minimum inhibitory concentration values. Various plant EOs have been effective against MRSA. Remarkably, lemongrass EOs completely inhibited all MRSA growth on the plate. Lemon myrtle, Mountain savory, Cinnamon bark and Melissa EOs showed a significant inhibition.

Conclusion: Several of these AMPs, EOs and their combinations were effective against MRSA. Their activities have implications for the development of new drugs for medical use.     

Cephalosporins in clinical development

Bacterial resistance to established classes of antibiotics in clinical use is continuing to increase, making the need for new agents that can be used to treat the newly multi-drug resistant organisms steadily more urgent. Cephalosporins have been a successful group of antibiotics since they were first introduced to combat drug-resistant organisms, including staphylococci. The history of cephalosporins has emphasised an improvement of their stability towards β-lactamases, thus expanding their spectrum of activity against important Gram-negative pathogens. New cephalosporins that have potent activity against multi-resistant Gram-positive bacteria, including methicillin-resistant staphylococci and penicillin-resistant pneumococci have recently entered clinical development. At least two of these, BAL-5788 and S-3578, also have Gram-negative activity, which is comparable to that of the third-and fourth-generation cephalosporins, making them broad-spectrum agents that could be used in hospital infections where methicillin-resistant staphylococci is likely to be present.     

Anti-folate based thymidylate synthase inhibitors

Thymidylate synthase (TS) is an essential enzyme in the de novo synthesis of thymidine, a pyrimidine nucleoside necessary for the synthesis and maintenance of integrity of DNA. Since 1950, a number of drugs have been discovered that have inhibitory effects on this enzyme. The most widely used are 5-fluorouracil (5-FU) and FUDR (floxuridine). Currently, several classes of newer and more specific TS inhibitors are under development in the hope of enhancing the efficacy and reducing the toxicity of these agents. Each new drug has unique structural and biologic characteristics which can be exploited to yield different clinical characteristics.