Indole/isatin-containing hybrids as potential antibacterial agents

The emergence and worldwide spread of drug-resistant bacteria have already posed a serious threat to human life, creating the urgent need to develop potent and novel antibacterial drug candidates with high efficacy. Indole and isatin (indole-2,3-dione) present a wide structural and mechanistic diversity, so their derivatives possess various pharmacological properties and occupy a salient place in the development of new drugs. Indole/isatin-containing hybrids, which demonstrate a promising activity against a panel of clinically important Gram-positive and Gram-negative bacteria, are privileged scaffolds for the discovery of novel antibacterial candidates. This review, covering articles published between January 2015 and May 2020, focuses on the development and structure–activity relationship (SAR) of indole/isatin-containing hybrids with potential application for fighting bacterial infections, to facilitate further rational design of novel drug candidates.     

病原菌耐药性与抗菌药物消耗量相关性的研究进展

病原菌耐药性是指细菌使抗菌药物治疗作用下降的一种状态。耐药菌的出现使临床感染性疾病的治疗难度增加,抗菌药物的不合理使用是细菌耐药产生的主要原因,全国范围内或区域医疗机构内有效的抗菌药物管理策略,能够减少抗菌药物使用并逆转细菌耐药性的产生。国内外有关抗菌药物使用与病原菌耐药性相关性的研究较多,国内缺少对全国性或区域性的研究数据。通过综述近年来国内外有关金黄色葡萄球菌、粪肠球菌、屎肠球菌、大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌、鲍曼不动杆菌、阴沟肠杆菌及其他病原菌的耐药性与常用抗菌药物消耗量的相关性,从宏观数据上把握两者间的关系,以期为医院感染的管理提供证据支持。     

皖南医学院第二附属医院抗菌药物专项整治前后抗菌药物的使用情况分析

目的调查皖南医学院第二附属医院抗菌药物专项整治前后抗菌药物的使用情况,以促进临床合理应用抗菌药物。方法调取皖南医学院第二附属医院2011、2015年抗菌药物的相关信息,对用药频度(DDDs)、用药金额、使用强度(AUD)、限定日费用(DDC)进行回顾性调查,并评价其合理性。结果抗菌药物专项整治后,抗菌药物的DDDs和用药金额均较整治前显著增加,DDDs和用药金额均增加较多的有大环内酯类,下降较多的为第4代头孢菌类;抗菌药物的AUD和DDC分别较整治前显著下降,下降较多的均为第4代头孢菌类。不合理用药现象较多为预防用药疗程长、选择药物不适宜、联合用药不适宜、无指征用药和预防用药时机不适宜,但整治后不合理率均较整治前明显降低。结论皖南医学院第二附属医院抗菌药物专项整治活动促使抗菌药物的AUD和不合理率明显下降,对不合理用药管制较有成效。     

2013—2016年海口市第一八七医院四肢创伤性骨折感染病原菌的分布及其耐药性分析

目的 探讨2013—2016年海口市第一八七医院四肢创伤性骨折感染病原菌的分布和耐药性情况,为临床合理用药提供依据.方法 对海口市第一八七医院2013年3月—2016年3月收治的四肢创伤性骨折住院患者3841例进行回顾性分析,收集病原菌感染的83例患者的资料,对其病原菌的分布及药敏结果进行回顾性分析.结果 共分离出病原菌89株,其中革兰阴性菌28株,构成比为31.46%,主要为大肠埃希菌、阴沟肠杆菌、肺炎克雷伯菌、铜绿假单胞菌和产气肠杆菌;革兰阳性菌61株,构成比为68.54%,主要为金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌和鸟肠球菌.大肠埃希菌对氨苄西林、左氧氟沙星、舒巴坦、超广谱β内酰胺酶、头孢曲松、头孢唑啉的耐药率为70.00%~100.00%;而对厄他培南、哌拉西林、丁胺卡那霉素、红霉素、亚胺硫霉素敏感.阴沟肠杆菌对亚胺硫霉素的耐药率为0.00%,对其他抗菌药物的耐药率为25.00%~100.00%.革兰阳性菌中金黄色葡萄球菌和表皮葡萄球菌均对氨苄西林、达福普丁、利奈唑胺、替加环素、呋喃妥因敏感,表皮葡萄球菌还对环丙沙星敏感,耐药率为0.00%;两者对青霉素均不具有耐药性,耐药率为100.00%.此外,两者对其他的抗菌药物耐性率均不达50.00%.结论 海口市第一八七医院四肢创伤性骨折感染病原菌以革兰阳性菌为主,临床应结合药敏试验,合理选用抗菌药物;同时要重视加强细菌耐药性的检测.     

2013-2015年宝鸡市中心医院不同年龄段住院患者病原菌的分布及耐药性分析

目的 了解宝鸡市中心医院不同年龄段患者的病原菌分布及对常用抗菌药物的耐药性.方法 将宝鸡市中心医院2013年1月—2015年12月病原菌培养阳性的住院患者,按照0~14岁、15~64岁、≥65岁分为3个不同的年龄阶段,对3个年龄段患者病原菌的分布及其耐药情况进行统计与分析.结果 共分离出病原菌4077株,主要来源于呼吸道和尿,其中革兰阳性菌702株,占17.2%,主要为葡萄球菌中的金黄色葡萄球菌、凝固酶阴性葡萄球菌和肠球菌中的粪肠球菌和屎肠球菌;革兰阴性菌3375株,占82.8%,主要为肠杆菌中的大肠埃希菌、肺炎克雷伯菌和非发酵菌中的铜绿假单胞菌、鲍曼不动杆菌.大肠埃希菌、铜绿假单胞菌、鲍曼不动杆菌、金黄色葡萄球菌及肠球菌等多种病原菌对抗菌药物的耐药率随着患者年龄的增长而增高.结论 不同年龄住院患者的病原菌分布及其耐药性有所不同,抗感染治疗时应充分考虑患者的年龄因素,合理使用抗菌药物.     

水飞蓟宾及其同分异构体的抑菌谱及其与抗生素联合抑菌效应探讨

目的探讨水飞蓟宾及同分异构体的体外抗菌谱及水飞蓟宾与临床常用抗生素的联合抑菌效应。方法用微量肉汤稀释法测定水飞蓟宾及同分异构体对临床感染常见细菌的6种标准菌株和6种临床分离菌株(74株)的最低抑菌浓度(MIC)。用平板菌落计数法测定不同质量浓度水飞蓟宾对6种标准菌株的生长抑制曲线。用棋盘微量肉汤稀释法进行水飞蓟宾与临床常用抗生素的联合药敏试验,计算联合抑菌指数(FIC),判定水飞蓟宾与抗生素的联合抑菌效应。结果水飞蓟宾对表皮葡萄球菌、金黄色葡萄球菌、粪肠球菌和屎肠球菌标准菌株的MIC为50~400μg/m L,对大肠埃希菌和铜绿假单胞菌标准菌株的MIC均400μg/m L;对表皮葡萄葡萄球菌临床分离菌株的MIC分别为100、200、400、400μg/m L,对金黄色葡萄球菌、粪肠球菌和屎肠球菌临床分离菌株的MIC分别为400、400μg/m L;对大肠埃希菌和铜绿假单胞菌临床分离菌株的MIC均400μg/m L。水飞蓟宾其他同分异构体对6种标准菌株的MIC为≥400μg/m L。水飞蓟宾对表皮葡萄球菌、金黄色葡萄球菌、粪肠球菌和屎肠球菌标准菌株的生长曲线都有明显抑制作用,抑制效果随药物质量浓度增加而增加,对大肠埃希菌和铜绿假单胞菌标准菌株的生长曲线无影响。水飞蓟宾与青霉素/红霉素联用对革兰阳性试验菌的FIC以0.5FIC≤1和1FIC≤2为主,水飞蓟宾与环丙沙星或庆大霉素联用对革兰阴性试验菌的FIC以FIC2或1FIC≤2为主。结论水飞蓟宾对革兰阳性菌有较好的抑菌活性,其中对表皮葡萄球菌抑菌活性最强。水飞蓟宾的抑菌活性明显高于其他同分异构体。水飞蓟宾与青霉素/红霉素联用主要为相加和无关作用,与环丙沙星或庆大霉素联用主要为拮抗或无关作用。     

核桃多类型化学物质研究进展及产业开发现状与发展途径

核桃Juglans regia主要含有多糖、黄酮、酚酸、皂苷、酯和醌类等多种化合物,具有抑菌、抗氧化、抗肿瘤、降血糖等作用,不仅可用于药物或功能性食品的开发,在食品行业等领域也具有良好应用基础和市场前景,这些活性物质是核桃中极具开发潜能的资源性物质。本文针对核桃的化学成分及其药理作用进行系统梳理,并在此基础上对其产业应用与发展途径进行了分析,以期为我国核桃资源的开发利用提供依据。     

大叶山楝萜类化学成分及其生物活性研究进展

大叶山楝Aphanamixis grandifolia为楝科山楝属植物,具有舒筋活络、通痹及祛风除湿等功效。大叶山楝中含有柠檬苦素类衍生物、甘遂烷型三萜、达玛烷型三萜、环阿尔廷烷型三萜、二萜及倍半萜等萜类化合物,具有杀虫、抗肿瘤、抗炎、抗疟疾和抑菌等生物活性。对大叶山楝萜类化学成分及其生物活性研究进展进行综述,以期为该植物的研究和开发利用提供参考。     

Primer containing dimethylaminododecyl methacrylate kills bacteria impregnated in human dentin blocks

Antibacterial dimethylaminododecyl methacrylate (DMADDM) was recently synthesized. The objectives of this study were to:(1) investigate antibacterial activity of DMADDM-containing primer on Streptococcus mutans impregnated into dentin blocks for the first time, and (2) compare the antibacterial efficacy of DMADDM with a previous quaternary ammonium dimethacrylate (QADM). Scotchbond Multi-Purpose (SBMP) bonding agent was used. DMADDM and QADM were mixed into SBMP primer. Six primers were tested:SBMP control primer P, P+2.5%DMADDM, P+5%DMADDM, P+7.5%DMADDM, P+10%DMADDM, and P+10%QADM. S. mutans were impregnated into human dentin blocks, and each primer was applied to dentin to test its ability to kill bacteria in dentinal tubules. Bacteria in dentin were collected via a sonication method, and the colony-forming units (CFU) and inhibition zones were measured. The bacterial inhibition zone of P+10%DMADDM was 10 times that of control primer (Po0.05). CFU in dentin with P+10%DMADDM was reduced by three orders of magnitude, compared with control. DMADDM had a much stronger antibacterial effect than QADM, and antibacterial efficacy increased with increasing DMADDM concentration. Dentin shear bond strengths were similar among all groups (P40.1). In conclusion, antibacterial DMADDM-containing primer was validated to kill bacteria inside dentin blocks, possessing a much stronger antibacterial potency than the previous QADM. DMADDM-containing bonding agent was effective in eradicating bacteria in dentin, and its efficacy was directly proportional to DMADDM mass fraction. Therefore, DMADDM may be promising for use in bonding agents as well as in other restorative and preventive materials to inhibit bacteria.     

Enhanced biocompatibility and antibacterial property of polyurethane materials modified with citric acid and chitosan

Citric acid (CA) and chitosan (CS) were covalently immobilized on polyurethane (PU) materials to improve the biocompatibility and antibacterial property. The polyurethane pre-polymer with isocyanate group was synthesized by one pot method, and then grafted with citric acid, followed by blending with polyethersulfone (PES) to prepare the blend membrane by phase-inversion method so that chitosan can be grafted from the membrane via esterification and acylation reactions eventually. The native and modified membranes were characterized by attenuated total reflectance-Fourier transform infrared spectroscope, X-ray photoelectron spectroscopy, scanning electron microscopy, water contact angle measurement, and tensile strength test. Protein adsorption, platelet adhesion, hemolysis assay, activated partial thromboplastin time, prothrombin time, thrombin time, and adsorption of Ca²⁺ were executed to evaluate the blood compatibility of the membranes decorated by CA and CS. Particularly, the antibacterial activities on the modified membranes were evaluated based on a vitro antibacterial test. It could be concluded that the modified membrane had good anticoagulant property and antibacterial property.