阿奇霉素4″-取代亚苄肼基甲酸酯衍生物的合成和抗菌活性

以阿奇霉素11，12-环硼酸酯为原料．设计并合成了18个阿奇霉素4″-取代亚苄肼基甲酸酯及4″-取代亚苄肼基甲酸酯．11，12-环碳酸酯衍生物。体外抗菌活性试验结果表明，所得化合物对受试革兰阳性菌如金黄色葡萄球菌、表皮葡萄球菌、白色葡萄球菌和肺炎双球菌抗菌活性良好，部分化合物对丙型链球菌、革兰阴性菌如鲍氏志贺氏菌和普通变形杆菌也有较强的抗菌活性。     

阿奇霉素衍生物的合成及抗菌活性Ⅱ.4"-取代酰基肼基甲酸酯

分别以阿奇霉素11,12-环硼酸酯和阿奇霉素为原料,设计并合成了22个阿奇霉素4"-取代酰基肼基甲酸酯及4"-取代酰基肼基甲酸酯-11,12-环碳酸酯衍生物.体外抗菌活性试验结果表明,所得大部分化合物对受试革兰阳性金黄色葡萄球菌和肠球菌抗菌活性良好,部分化合物对革兰阳性表皮葡萄球菌、丙型链球菌和革兰阴性福氏志贺菌也有较强的抗菌活性.     

阿奇霉素衍生物的合成和抗菌活性研究.Ⅲ.4"-取代亚乙基肼基甲酸酯

以阿奇霉素11,12-环硼酸酯为原料,设计并合成了17个阿奇霉素4"-取代亚乙基肼基甲酸酯及4"-取代亚乙基肼基甲酸酯-11,12-环碳酸酯衍生物.体外抗菌活性试验结果表明,目标化合物对受试表皮葡萄球菌、白色葡萄球菌、肺炎双球菌和丙型链球菌等革兰阳性菌,以及福氏志贺菌等革兰阴性菌抗菌活性良好,部分化合物对革兰阳性金黄色葡萄球菌和肠球菌也有较强的抗菌活性.     

阿奇霉素衍生物的合成和抗菌活性研究.Ⅳ.4"-取代杂芳环亚甲基肼基甲酸酯

以阿奇霉素11,12-环硼酸酯为原料,设计并合成了13个阿奇霉素4"-取代杂芳环亚甲基肼基甲酸酯及4"-取代杂芳环亚甲基肼基甲酸酯-11,12-环碳酸酯衍生物.体外抗菌活性试验结果表明,目标化合物对金黄色葡萄球菌、表皮葡萄球菌、白色葡萄球菌、肺炎双球菌和丙型链球菌等革兰阳性菌,以及福氏志贺菌等革兰阴性菌抗菌活性良好.     

红霉素环11,12-碳酸酯的体外抗菌活性研究

目的评 价红霉素环11，12-碳酸酯的体外抗菌活性。方法 采用琼脂平皿二倍稀释法测定国产和进口红霉素环11，12-碳酸酯对临床分离致病菌的体外抗菌作用，并与红霉素、罗红霉素、克拉霉素、地红霉素、阿奇霉素和乙酰螺旋霉素进行了比较。结果 国产和进口红霉素环11，12-碳酸酯对579株临床分离菌的抗菌活性相近，对革兰氏阳性菌和厌氧菌的抗菌活性比红霉素强2～8倍，优于罗红霉素、克拉霉素、地红霉索、阿奇霉素、乙酰螺旋霉素，但对革兰氏阴性菌的抗菌活性稍弱于阿奇霉素。红霉索环11，12-碳酸酯对金葡菌显示抑菌作用，对化脓链球菌在2～4倍MIC浓度时显示杀菌作用；红霉素环11，12-碳酸酯抗金葡菌和化脓链球菌的活性随着pH的增加而增强，接种量和血清浓度对国产红霉素环11，12-碳酸酯抗金葡菌和化脓链球菌的活性无明显影响。结论 红霉素环11，12-碳酸酯具有较强的体外抗菌活性，国产红霉素环11，12-碳酸酯抗菌活性与进口相近，优于红霉素、罗红霉素、克拉霉素、地红霉素、阿奇霉素和乙酰螺旋霉素。     

阿奇霉素的药理作用与临床应用

目的 经临床实践和有关资料总结评价阿奇霉素的抗菌谱，药效及合理用药范围，以利于临床应用。方法 应用阿奇霉素对不同致病菌所致疾病进行疗效观察。结果 阿奇霉素对大多数革兰阳性菌和一些革兰阴性菌抗菌活性高，并能抑制多种革兰阳性球菌，支原体、衣原体及嗜肺军团菌，尤其是对一些重要的革兰阴性杆菌，如流感嗜血杆菌等具有良好的抗菌活性，弥补了大环内酯类对嗜血杆菌作用差的不足，且不良反应小。结论 阿奇霉素是治疗以上致病菌引起的呼吸道感染、皮肤及软组织感染，泌尿及生殖系统及其他性传播疾病的首选药物。     

环酯红霉素对近5年临床分离菌株的体外敏感性研究

目的通过比较近五年临床分离菌株对多种抗菌药物的药物敏感性及耐药性研究,了解环酯红霉素的体外抗菌活性。方法利用琼脂平板稀释法对临床分离220株细菌进行药敏性分析。结果药物敏感性实验表明肺炎链球菌、化脓链球菌、金黄色葡萄球菌、表皮葡萄球菌和流感嗜血菌对环酯红霉素的耐药率分别为35.0%、55.0%、35.0%、36.7%和70.0%。肺炎链球菌、化脓链球菌、金黄色葡萄球菌、表皮葡萄球菌和流感嗜血菌对环酯红霉素的MIC50和MIC90分别为1、1、32、0.5、64μg/mL和32、8、256、32、128μg/mL。结论经SPSS17.0统计分析后,发现临床分离菌株对环酯红霉素和阿奇霉素的耐药率表明两者的抗菌活性相当,不存在统计学差异(P>0.05)。     

阿奇霉素治疗儿童呼吸道感染100例临床分析

阿奇霉素（azithromycin）是一种新的红霉素衍生物，其抗菌谱增宽，不仅对临床上常见的主要致病菌如：G^＋革兰阳性、G^-革兰阴性菌，厌氧菌、金黄色葡萄球菌、肺炎双球菌有高度的杀菌活性，对于非典型肺炎：衣原体、军团菌肺炎也为首选药物，对肺炎支原体的作用是大环内酯类中最强的。阿奇霉素虽经肝脏代谢，但他大量由粪便排泄，目前国内外尚无见其肝、肾损害的报道。近年来阿奇霉素已陆续用于儿科临床，治疗儿童呼吸道感染效果较好，现报告如下。     

阿奇霉素缓释片的研制

阿奇霉素（ａｚｉｔｈｒｏｍｙｃｉｎ，１）是第一个１５元环大环内酯类抗生素，除对革兰阳性菌有较好的抗菌作用外，尤其对革兰阴性菌中的流感嗜血杆菌、淋病奈瑟氏球菌有很强的抗菌作用，对某些阴性杆菌如大肠杆菌的抗菌作用也强于红霉素［１］。临床主要用于非并发性皮...     

淋球菌对阿奇霉素耐药性与耐药机制研究进展

阿奇霉素是15元环大环内酯类抗生素,其结构与红霉素相似,但在内酯环的9位上杂入了一个甲氨基。阿奇霉素的抗菌谱广,不仅对革兰阳性球菌、厌氧菌、支原体、衣原体有作用,对一些革兰阴性菌,包括流感嗜血菌、淋球菌等也有较好的作用,且对淋球菌的作用比红霉素强4倍。淋球菌为严重的人体寄生菌,常存在于急性尿道炎与阴道炎的脓性分泌物白细胞中,是引发淋病的病原体。如今,淋球菌正在对越来越多种类的抗生素产生耐药性,阿奇霉素便是其中一种。然而,淋球菌对阿奇霉素产生耐药性的机制尚不明确,有研究表明其机制可能与mtr系统有关。本文主要对一些国家出现的淋球菌对阿奇霉素的耐药性及其机制进行了概述。     

Synthesis and antibacterial activity of new 4″-O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether

A series of new 4″-O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether were synthesized and evaluated for their in vitro antibacterial activity. All the desired compounds demonstrated favorable activity (0.03 μg ml(-1)) against erythromycin-susceptible Streptococcus pneumoniae comparable to the references, exhibiting 133-fold higher activity than precursor 2 or 3. Similarly, all of the analogs exhibited improved activity against the erythromycin-resistant S. pneumoniae encoded by the erm gene and the erm and mef genes, showing 4-32-fold more effectiveness than erythromycin A.     

Synthesis and antibacterial activity of the tricyclic ketolides TE-802 and its analogs

The novel 6-O-methyl tricyclic ketolides TE-802 and its analogs were synthesized by two successive cyclization reactions, 11,12-cyclic carbamate formation by intramolecular Michael addition and 9,11-diazaheptene ring construction by intramolecular dehydration reaction. These new tricyclic ketolides exhibited good in vitro antibacterial activity against not only erythromycin-susceptible strains but also erythromycin-resistant Staphylococcus aureus and Streptococcus pneumoniae, which are problematic pathogens of nosocomial and community-acquired respiratory tract infections, respectively.     

Synthesis and antibacterial activity of a novel series of acylides: 3-O-(3-pyridyl)acetylerythromycin A derivatives

A novel series of acylides, 3-O-(aryl)acetylerythromycin A derivatives, were synthesized and evaluated. These compounds have significant potent antibacterial activity against not only Gram-positive pathogens, including inducibly macrolide-lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but also Gram-negative pathogens, such as H. influenzae. 6,9:11,12-dicarbonate acylide 47 (FMA0122) was twice as active against H. influenzae than azithromycin, whereas it showed only moderate in vivo efficacy in mouse protection tests. However, the 11,12-carbamate acylide 19 (TEA0929), which showed potent antibacterial activity against almost all of the main causative pathogens of community-acquired pneumonia tested, exhibited excellent in vivo efficacy comparable to those of second-generation macrolides.     

Erythromycin A 11,12-methylene acetal

Erythromycin A 11,12-methylene acetal (5) and the corresponding 9-methoxime, 9-dihydro, and 8-hydroxy derivatives have been prepared and their antibacterial activities compared with those of erythromycin A and its 11,12-cyclic carbonate. The simple methylene acetal 5 showed excellent activity against Gram-positive organisms in vitro.     

Synthesis and antibacterial activity of isomeric 15-membered azalides

A series of 3-keto and 3-O-acyl derivatives of both 6-O-alkyl-8a-aza-8a-homoerythromycin A and 6-O-alkyl-9a-aza-9a-homo-erythromycin A were synthesised and tested against Gram-positive and Gram-negative bacteria. Derivatives of 8a-aza-8a-homoerythromycin A have potent antibacterial activity against not only azithromycin-susceptible strains, but also efflux (M) and inducible macrolide-lincosamide-streptogramin (iMLSB) resistant Gram-positive pathogens, while the corresponding 9a-isomers were less active. Introduction of an additional ring such as 11,12-cyclic carbonate reduced antibacterial activity of both series. 3-Keto and 3-O-(4-nitrophenyl)-acetyl derivatives of 6-O-methyl-8a-aza-8a-homo-erythromycin A show typical macrolide pharmacokinetics in preliminary in vivo studies in mice, and their in vivo efficacy is demonstrated.     

阿奇霉素新衍生物的设计、合成及抗病毒活性

目的利用阿奇霉素的体内分布特点,设计了新的阿奇霉素衍生物,寻找具抗病毒活性的新化合物。方法利用O₂计算机辅助药物设计工作站,设计并合成新阿奇霉素衍生物,用抗乙肝病毒药物筛选模型进行了药理活性研究。结果设计合成了3个新的阿奇霉素衍生物和两个新中间体,目的物4a,4b,5经波谱分析结构准确。药理活性结果表明化合物具抗病毒活性。结论化合物4b具很好的抗病毒活性。证实化合物设计思路正确,可以指导类似化合物的设计。     

Cytotoxic and antibacterial flavonoids from dragon's blood of Dracaena cambodiana

Chemical studies on the constituents from the dragon's blood of Dracaena cambodiana led to the discovery of three new flavonoid derivatives (1- 3) and six known compounds (4- 9). The structures of the three new compounds were elucidated by NMR and MS spectroscopic analyses. All compounds were evaluated for their growth inhibitory activity against human cell lines K-562, SMMC-7721, and SGC-7901, as well as antibacterial activities against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). As a result, compounds 1, 2, 5, 7, and 9 showed cytotoxicity against K-562, SMMC-7721, and SGC-7901 cell lines. All these compounds were observed to exhibit antibacterial activities against S. aureus, and compounds 1- 4, 6, 8, and 9 were observed to exhibit antibacterial activity against MRSA.