唑类抗真菌药物结构修饰的研发进展

唑类药物是治疗真菌感染的主要用药，按化学结构分为咪唑类和三唑类。现综述了唑类药物近年来结构修饰和构效关系的研究进展，为进一步的新药研究提供线索。     

鹿蹄草化学成分研究

目的：研究鹿蹄草Pyrola calliatha全草的化学成分。方法：采用硅胶及Sephadex LH-20凝胶柱色谱法等分离化合物,运用波谱学方法确定结构；并对化合物1～4,6～9进行抗真菌活性测定。结果：从鹿蹄草全草中分离得到10个化合物,分别为梅笠草素(1),熊果醇(2),熊果酸(3),2β,3β,23-三羟基-12-烯-28-乌苏酸(4),胡萝卜苷(5),2α,3β,23,24-四羟基-12-烯-28-乌苏酸(6),大黄素(7),没食子酸(8),水晶兰苷(9),腺苷(10)。结论：化合物2,4,6,7,10为首次从该属植物中分离得到,化合物5,9为首次从该种植物中分离得到；化合物1,3,4,6,8对新生隐球菌、白色念珠菌、红色毛癣菌等真菌生长有不同的抑制作用,其中化合物1的抗真菌活性较强。     

支原体培养基中真菌抑菌剂的筛选

目的 为支原体的培养基筛选一种抗真菌的药物,以防止真菌污染。方法 在五种备选药物中先找出不抑制支原体生长但是能够有效抑制真菌生长的药物。再选用20株白色念珠菌的临床株,各测此种药物对其MIC,最后得出MIC50与MIC90,选用MIC90的浓度加于支原体的培养基中。结果 最后选出的药物为氟康唑,用20临床株测得MIC50为15.6μg/ml,MIC90为31.25μg/ml结论选用浓度为31.25μg/ml的氟康唑加于支原体的培养基可以有效抑制白色念珠菌的生长。     

146例医院真菌感染的特点及其耐药分析

目的探讨146例传染病患者医院真菌感染的特点及药敏情况。方法对2003—2005年传染病住院患者中的真菌感染病例进行回顾性调查分析。结果医院真菌感染率从2003的1．16％上升到2005年的1．62％。感染的部位以消化道、口腔为主，分别占39．04％、32．88％。被检出真菌有19种，以白色假丝酵母菌、热带假丝酵母菌为主，分别占37．67％、26．71％，对抗真菌药物伊曲康唑、两性霉素B、氟康唑敏感，但敏感率在下降，对咪康唑、益康唑、酮康唑耐药率较高。感染的发生与病情危重、免疫功能紊乱、老龄化、使用广谱抗菌药物，以及各种侵入性诊疗技术等因素相关。结论真菌感染率呈逐年上升趋势，真菌的耐药性也逐渐增多。对各种危险因素采取综合措施．合理使用抗菌药物，是减少医院感染发生的关键。     

New systematically active antimycotics from the beta-blocker category

Beta-blocker
Summary. Candida albicans secretes phospholipases, which are considered to be one of the mediators of cell penetration. It is known that other phospholipases from mammalian cells can be inhibited by lipophilic beta-blocking structures. As the result of a synthesis programme of several years' duration, structures deriving from β-hydroxyethylamines were introduced. In vitro and in vivo results with these compounds are presented in comparison with standard antimycotics. In combination with fluconazole, several of the compounds can prevent death in mice infected with lethal inocula of C. albicans. Histological examinations confirm the inhibitory effect of the beta-blocker-like scructures on tissue penetration. The structures therefore constitute new antimycotics that are endowed with extensive in vitro effectiveness against fungi and also definite in vivo effects in the animal model.
Zusammenfassung. Candida albicans sezerniert Phospholipasen, der als Vermittler der Zellpenetration diskutiert werden. Von anderen Phospholipasen aus Säugerzellen ist bekannt, daß sie durch lipophile β-blockierende Strukturen hemmbar sind. Als Ergebnis eines mehrjährigen Synthese-programms werden Strukturen vorgestellt, die sich von β-Hydroxyethylaminen ableiten. In vitro und in vivo Ergebnisse mit diesen Verbindungen werden im Vergleich zu Standardantimykotika vorgestellt. In Kombination mit Fluconazol führen einzelne der Verbindungen zum Überleben von Mäusen, die mit letalen Inokula von C. albicans infiziert worden waren. Histologische Untersuchungen bestätigen den hemmenden Einfluß der β-Blocker-artigen Strukturen auf die Gewebepenetration. Die Strukturen stellen somit neue Antimykotika dar, die über eine breite in vitro Wirksamkeit gegenüber Pilzen wie auch über deutliche in vivo Wirkungen im Tiermodell verfügen.     

In vitro antifungal activity of Polyporaceae against yeasts and dermatophytes

Summary. The antifungal activity of 38 Polyporaceae sensu lato against yeasts and dermatophytes was tested in vitro by the agar dilution method. Strains were typed organisms and clinical isolates. In this first report Pycnoporellus fulgens (Fr. Donk was found to be the most active species against pathological fungi and showed broad-spectrum antifungal activity against yeasts ( Candida albicans, Candida glabrata ) and dermatophytes ( Trichophyton mentagrophytes, Trichophyton rubrum. Microsporum canis. Microsporum gypseum. Epidermophyton floccosum ). Other Polyporaceae species also showed antifungal activity, but only against dermatophytes.
Zusammenfassung. Alkoholische Rohextrakte von 38 Polyporaceae-Arten wurden in vitro mittels Agardilutiontest auf ihre antimyzetische Wirkung gegen Hefen und Dermatophyten geprüft. Die Teststämme waren einige Sammlungsstämme, in der Mehrzahl aber klinische Isolate. In dieser Studie erwies sich der Extrakt von Pycnoporellus fulgens (Fr.) Donk als antimyzetisch aktivste Spezies gegen pathogene Hefen ( Candida albicans, C. glabrata ) sowie gegen Dermatophyten ( Trichophyton mentagrophytes, T. rubrum, Microsporum canis, M. gypseum, Epidermophyion floccosum ). Andere Polyporaceae zeigten ebenfalls antimyzetische Aktivitat, jedoch nur gegen Dermatophyten.     

Susceptibility of clinical isolates of Fusarium to antifungal drugs

Summary. The inhibitory activities of amphotericin B, fluconazole, itraconazole, miconazole, ketoconazole and terbinafine against nine isolates from clinically apparent infections of Fusarium solani , four isolates of Fusarium moniliforme and 10 isolates of Fusarium oxysporum were determined with an agar diffusion method (Neo-sensitabs) and an agar dilution method. The inhibition zones obtained with antifungal Neo-sensitabs need very careful interpretation. We did not find a good correlation between the agar diffusion method using Neo-sensitabs preloaded with azoles and amphotericin B and the agar dilution method. Amphotericin B (12/23) and terbinafine (18/23) showed good activity. Miconazole (7/23) and ketoconazole (3/23) had poor inhibitory activity. Fluconazole and itraconazole (0/23) had no in vitro activity against any of the isolates tested.
Zusammenfassung. Die inhibitorische Aktivität von Amphotericin B, Fluconazol, Itraconazol, Miconazol, Ketoconazol und Terbinafin gegen 9 klinische Isolate von Fusarium solani , 4 von Fusarium moniliforme und 10 von Fusarium oxysporum wurde mit einer Agar-Diffusionstechnik (Neo-sensitabs) und einer Agar-Dilutionsmethode untersucht. Die Hemmhöfe mit Neo-sensitabs müssen mit Vorsicht interpretiert werden. Es wurde keine gute Korrelation zwischen der Agar-Diffusionstechnik mit Neo-sensitabs, beladen mit Azolen und Amphotericin B, und der Agar-Dilutionstechnik gefunden. Amphotericin B (12/23) und Terbinafin (18/23) zeigen eine gute Aktivität. Miconazol (7/23) und Ketoconazol (3/23) haben nur schwache inhibitorische Aktivität. Fluconazol und Itraconazol (0/23) zeigen in vitro keine Aktivität gegen die untersuchten Fusarium -Stämme.     

Screening of some indigenous Qatari medicinal plants for antimicrobial activity

Aqueous, ethanol and butanol crude extracts of the aerial parts of ten plants exhibited variable degrees of antimicrobial activity against four bacterial and two fungal species. Aqueous extracts had low antimicrobial activity against E.coli, P.aeruginosa, B. cerreus, S.aureus, C.albicans and A.flavus. Avicennia marina (AM) aqueous extract exhibited a moderate antifungal activity. Ethanol and butanol crude extracts exhibited an improved antimicrobial activity. However, butanol exhibited a superior antimicrobial activity compared with aqueous and ethanol crudes. Compared with the standard antibiotics tested the butanol extract had the highest activity. Butanol extracts at 2000 microg/disc of AM, Lotus halophilus (LA), Pulicaria gnaphaloides (PG) and Capparis spinosa (CS) had a very good antibacterial activity against both gram-positive and -negative bacteria as well as moderate to good antifungal activity against C. albicans and A. flavus. Medicago laciniata (ML), Limonium axillare (LA) and (PG) butanol crude extract compared with standard chloramphenicol, tetracycline and nalidixic acid exhibited a superior antifungal activity.     

Antimicrobial potential of two different Hypericum species available in India

The antimicrobial activity of extracts of the leaves and stems of two different varieties of Hypericum was evaluated by the disc diffusion method. Petroleum ether, acetone, chloroform and methanol extracts of Hypericum mysorense and Hypericum patulum stems and leaves were investigated for their antimicrobial activity against six different strains of bacteria and fungi by the zone of inhibition method (ZIM). The results showed that both the stem and leaf extracts of both species have a very broad spectrum of antibacterial activity. The petroleum ether and acetone extract of the leaves and stems of H. mysorense did not show antifungal effects against any of the six fungal organisms tested but other extracts showed a potential antifungal effect which was comparable to that of griseofulvin, the standard antifungal agent. Thus these results demonstrate that the leaf and stem extracts of both the Hypericum species have a very broad spectrum of activity and suggest that they may be useful in the treatment of various microbial infections.     

Influence of voriconazole and fluconazole on Candida albicans in long-time continuous flow culture

We investigated the influence of voriconazole and fluconazole in a long term trial of continuous flow culture (cfc) up to 9 days. The effects of these azoles were different in dependence on the growth circumstances. Under anaerobic conditions a fungicidal effect of voriconazole was detectable, defined by an inhibition of 99.9%. This also applied to fluconazole for the majority of tested strains of C. albicans. Under aerobic conditions with an otherwise similar situation we found only a fungistatic reaction (inhibition of 90%). Fluorescence microscopy comparing fungal morphology in biofilms on glass surfaces in the cfc revealed a differentiation into blastospores, germ tubes, pseudomycelia and mycelia in the control trial after a cultivation of 8 days. Under anaerobic conditions with azoles only some single cells could be found, sometimes in cell detritus. The adhesion was clearly reduced. Under aerobic conditions more blastospores but no differentiated mycelia were to be seen.