3-氯代亚甲基色满-4-酮类化合物的设计、合成及体外抗真菌活性研究

本文以取代苯酚为原料,经微波条件下的取代反应和多聚磷酸中进行的环合反应制备了取代色满酮,取代色满酮与甲酸乙酯的缩合产物经氯化反应制备了3-氯代亚甲基色满-4-酮类化合物,共合成了10种未见文献报道的新化合物。化合物结构经质谱和核磁共振氢谱进行了确证,并且采用二倍稀释法对目标化合物的体外抗真菌活性进行了测试,结果表明它们具有很好的体外抗真菌活性,其中化合物4c、4e、4g和4h对石膏样小孢子菌的MIC值为1μg.mL1,高于对照药氟康唑和两性霉素B,具有进一步研究价值。     

浙新霉素对皮肤癣菌的体外抗真菌活性研究

目的：评价浙新霉素体外抗真菌活性。方法：采用CLSI推荐的M-38A方案测定浙新霉素对7种皮肤癣菌最小抑菌浓度（MIC）及最小杀菌浓度（MFC）。结果：浙新霉素对7种皮肤癣菌的MIC范围为0.125-2.000μg·ml^-1,MFC范围为0.250-4.000μg·ml^-1。结论：浙新霉素具有较强的抗真菌活性,能抑制和杀灭絮状表皮癣菌、红色毛癣菌、紫色毛癣菌、犬小孢子菌、须癣毛癣菌、断发毛癣菌、石膏样小孢子菌等多种皮肤癣菌。     

氮唑类CYP51抑制剂的合成及体外抗真菌活性测定

目的:合成一系列1,2,4-三唑-3-硫酮衍生物并考察其体外抗真菌活性。方法:通过酯化、肼解、缩合、环化四步反应合成目标化合物。将待测化合物配成浓度为1.6 mg.m L~(-1)的药物原液,并通过2倍稀释法将其制备成10个不同梯度浓度的待测药液,使用微量稀释法测试这些化合物对白色念珠菌、孢子丝状真菌和絮状表皮藓菌三种真菌的抗菌活性。结果:得到17个1,2,4-三唑-3-硫酮的卤代苯基衍生物、烃基衍生物、吡啶衍生物。其中,化合物6h对白色念珠菌、孢子丝状真菌和絮状表皮藓菌菌株的最小抑菌浓度(MIC)值达到12.5、12.5、6.25μg.mL~(-1),化合物6d和6m对白色念珠菌的MIC值均为12.5μg.mL~(-1),与对照药物酮康唑的抑菌活性相当。化合物6a、6d、6m、6p对孢子丝状真菌的MIC值均为25μg.mL~(-1)。结论:1,2,4-三唑-3-硫酮衍生物具有不同程度的体外抗真菌活性,特别是化合物6h的抗菌效果显著,值得我们进一步研究以发展成为先导化合物。     

2,3,3a,4-四氢硫色烯并[4,3-c]吡唑类化合物的合成及其体外抗真菌活性研究

目的 设计合成2,3,3a,4-四氢硫色烯并[4,3-c]吡唑类化合物，并对其体外抗真菌活性进行初步评价。方法 以取代苯硫酚为起始原料，合成中间体3-次苄基硫色满酮，该中间体与水合肼在热醋酸中反应生成目标化合物。采用二倍稀释法对4种受试真菌—絮状表皮毛癣菌(E. floccosum)、石膏样小孢子菌(M. gypseum)、绿色木霉菌(T. viride)和断发毛癣菌(T. tonsurans)进行体外抗真菌活性测试。结果 合成了12个新的2,3,3a,4-四氢硫色烯并[4,3-c]吡唑类化合物，其结构经氢核磁共振谱、质谱和元素分析确证。抗真菌实验结果表明，所合成的目标化合物对供试真菌具有一定程度的抑制活性。结论 2,3,3a,4-四氢硫色烯并[4,3-c]吡唑类化合物具有体外抗真菌活性。     

中药"铁扇癣痒平"体外抑菌试验

目的观察"铁扇癣痒平"体外抗菌效果和抑菌浓度.方法采用对倍液体稀释法测定该药对金黄色葡萄球菌、大肠杆菌、红色毛癣菌、紫色毛癣菌、须毛癣菌和石膏样小孢子菌体外抑制作用.以市售的复方土槿皮酊、庆大霉素和二性霉素B为对照.结果体外抑菌试验结果表明,该药对细菌(金黄色葡萄球菌、大肠杆菌)和真菌(红色毛癣菌、紫色毛癣菌、须毛癣菌、石膏样小孢子菌)均有抑制作用.结论"铁扇癣痒平"具有体外抑制革兰阳性、革兰阴性细菌和皮肤真菌的作用,且抗真菌活性高于抗细菌活性.     

伪绵马酚及其衍生物的合成与体外抗真菌作用

目的设计合成伪绵马酚及其衍生物,并考察其抑菌活性。方法基于拼合原理,通过还原、傅-克酰基化等反应合成伪绵马酚及其衍生物并鉴定目标化合物的结构;采用M38-A2微量稀释法测定绵马酚、伪绵马酚及中间体对红色毛癣菌、须癣毛癣菌及犬小孢子菌的抑菌活性。结果与结论合成了伪绵马酚、4个中间体及2个伪绵马酚衍生物;活性研究表明,伪绵马酚对犬小孢子菌、须癣毛癣菌、红色毛癣菌3种皮肤癣菌的抗菌作用最强,其MIC值分别为10、20、28.28 mg·L~(-1)。结论合成的目标化合物对3种受试真菌均具有不同程度的抑制作用,可以为间苯三酚类化合物的成药研究提供理论基础。     

6,8——二氯硫色满酮衍生物的合成及抗真菌活性

６，８——二氯硫色满酮衍生物的合成及抗真菌活性方林郭春张国梁张炜设计并合成了１３个硫色满酮衍生物，其中１２个为未见文献报道的新化合物．对这些化合物进行了体外抑真菌活性测定，结果表明，对供试真菌均有不同程度的抑菌作用．6,8——二氯硫色满酮衍生物的合成及?..     

地锦草提取物抗真菌作用及对红色毛癣菌角鲨烯环氧化酶的影响

目的 对地锦草提取物（EHE）进行体外抗真菌实验,探讨其抗真菌作用机制。方法 采用美国临床实验室标准化委员会（NCCLS）推荐的《产孢丝状真菌的液基稀释法抗真菌药物敏感性试验方案》（M38 A）,测定地锦草提取物对82株临床常见真菌的最低抑菌浓度值（MIC）;酶联免疫吸附试验（ELISA）研究其对红色毛癣菌角鲨烯环氧化酶的影响。结果 地锦草提取物对红色毛癣菌的平均MIC为446 μg•mL 1,石膏样毛癣菌值的平均MIC为652 μg•mL 1,紫色毛癣菌的平均MIC为1 024 μg•mL 1,许兰毛癣菌的平均MIC为896 μg•mL 1,疣状毛癣菌平均MIC为853 μg•mL 1,犬小孢子菌及4种念珠菌的平均MIC均＞1 024 μg•mL 1;地锦草提取物256 μg•mL 1时,可显著降低红色毛癣菌中角鲨烯环氧化酶的活性（P＜0.01）。结论 地锦草提取物有显著的抗真菌活性,对皮肤癣菌的敏感性比念珠菌高;其抗真菌机制可能与抑制角鲨烯环氧化酶的活性有关。     

次氯酸钙抗真菌的体外实验与临床应用

目的探讨次氯酸钙的抗真菌作用及机制.方法采用琼脂双倍稀释法及中和剂悬液法培养对6种常见致病性真菌进行抑菌实验;观察最小抑菌浓度作用下,3种致病真菌的超微结构变化;随机分组比较次氯酸钙与克霉唑、制霉菌素治疗皮肤浅部真菌病的临床疗效.结果次氯酸钙对红色毛癣菌、石膏样小孢子菌、羊毛状小孢子菌、絮状表皮癣菌有抑制和杀灭作用,其最低抑菌稀释度为1∶400;对白色念珠菌和孢子丝菌均有抑制作用,最低抑菌稀释度分别为1∶100,1∶50;能破坏红色毛癣菌、石膏样小孢子菌及白色念珠菌的细胞壁,使细胞质、细胞核空泡化,细胞器变性;随机分组对比治疗皮肤浅部真菌病,其效果与对照组相似(P＞0.05).结论次氯酸钙具有抗真菌作用,能杀灭常见浅部致病真菌,抑制常见深部致病真菌.临床应用效果确切,副作用小,安全.     

大黄竹醋洗剂的制备及抗真菌作用研究

目的：研究大黄竹醋洗剂的制备工艺和对致病性真菌的抑制效应。方法采用平板培养基连续稀释法进行抑菌试验。结果大黄竹醋洗剂对絮状表皮癣菌、红色毛癣菌、须癣毛癣菌、石膏样毛癣菌、羊毛状小孢子菌、白色念珠菌、新生隐球菌、青霉菌有抑制作用,MIC为0.156～5mg· mL^ -1。结论大黄竹醋洗剂对某些真菌有一定的抑制,值得临床推广使用。     

Antifungal activity of magnolol and honokiol

Two neolignan compounds, magnolol (5,5'-diallyl-2,2'-dihydroxybiphenyl, 1) and honokiol (5,5'-diallyl-2,4'-dihydroxybiphenyl, 2), were isolated from the stem bark of Magnolia obovata and evaluated for antifungal activity against various human pathogenic fungi. Compound 1 and 2 showed significant inhibitory activities against Trichophyton mentagrophytes, Microsporium gypseum, Epidermophyton floccosum, Aspergillus niger, Cryptococcus neoformans, and Candida albicans with minimum inhibitory concentrations (MIC) in a range of 25-100 microg/ml. Therefore, compound 1 and 2 could be used as lead compounds for the development of novel antifungal agents.     

Chemical analysis and antifungal activity of the essential oil of Calea clematidea

The chemical composition of the essential oils of Calea clematidea Baker obtained by hydrodistillation of the leaves and flowers was analysed by GC and GC/MS and the oils were assayed for their antifungal activities. The essential oil of the leaves showed a high content of a new natural epoxy terpenoid, named clemateol (ca. 70 %), with minor amounts of o-vanillin (6.5 %), spathulenol (4.2 %), alpha-terpinene (4.0 %), germacrene B (2.9 %), yomogi alcohol (1.8 %), ( E)-caryophylene (1.7 %), m-cymenene (1.6 %), and alpha-gurjunene (1.5 %), while the essential oil of the flowers was characterized by a higher content of thymol methyl ether (ca. 80 %), with minor amounts of clemateol (4.8 %) and o-cymene (4.7 %). The antimicrobial activity of the oils was also evaluated against dermatophytes for their possible use in pharmaceutical preparations for topical applications. The oil of the leaves (MIC > 3.57 mg/ml), clemateol (MIC > 1.52 mg/ml), and the alcohol 2 (MIC > 2.82 mg/ml) showed a moderate antifungal activity against Trichophyton tonsurans, Trichophyton rubrum, Trichophyton menthagrophytes var. i nterdigitale, Epidermophyton floccosum, Microsporum gypseum, Microsporum canis and Microsporum nanum.     

土槿乙酸B体外抗真菌活性及对白色念珠菌麦角甾醇生物合成的影响

目的研究土槿乙酸B（PLAB）的体外抗真菌活性和对白色念珠菌细胞膜中麦角甾醇生物合成的影响.方法：采用微量液体稀释法研究PLAB 的体外抗白色念珠菌、新生隐球菌、絮状表皮癣菌的活性.将白色念珠菌经不同浓度PLAB 及氟康唑作用28 h 后,经过皂化、提取未皂化脂,采用高效液相色谱法测定其麦角甾醇的含量变化.结果：PLAB 对白色念珠菌、新生隐球菌、絮状表皮癣菌这三株菌株的MIC50分别为16、32、16 μg·mL-1.PLAB能使白色念珠菌中的麦角甾醇含量下降（P 〈0.05）,且含量变化呈明显的剂量依赖性.结论：PLAB 具有较强的抗真菌作用,通过抑制真菌的麦角甾醇生物合成而发挥高效抗真菌活性.     

In vitro antifungal activities of amorolfine against fresh isolates from patients with cutaneous mycosis

In vitro antifungal activities of amorolfine (MT-861), a new morpholine antifungal agent, were examined using an agar-dilution method, in comparison with those of 2 other antifungal agents, clotrimazole (CTZ) and bifonazole (BFZ), against 182 clinical isolates of Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, and Epidermophyton floccosum, which had been freshly isolated from a total of 182 cutaneous mycotic patients with various types of dermatophytes or cutaneous candidiasis. Antifungal activities of the 3 drugs against T. rubrum were in the order of MT-861 greater than CTZ greater than BFZ, with the lowest average MIC values (0.0070 micrograms/ml) obtained with MT-861. The average MIC value of MT-861 for clinical isolates from patients with pedis was roughly 2.3-fold higher than that for those from patients with tinea corporis. Out of 3 drugs tested MT-861 exhibited the most potent activities against clinical isolates of T. mentagrophytes, M. canis, and E. floccosum with average MIC values of 0.0267, 0.0079, and 0.0018 micrograms/ml, respectively. MIC values of MT-861 against isolates of Candida albicans ranged from 0.01 to 10 micrograms/ml, and the average value (0.1762 micrograms/ml) was the lowest of the 3 drugs.     

In vitro antifungal activity of itraconazole, a new triazole antifungal agent, against clinical isolates from patients with dermatomycoses]

In vitro antifungal activities of itraconazole (ITZ), a triazole antifungal agent, against clinical isolates obtained from patients with superficial and subcutaneous mycoses were examined using the agar dilution method on casitone agar. The clinical isolates tested were 7 species and 263 isolates including Trichophyton mentagrophytes (104 isolates), Trichophyton rubrum (103 isolates), Microsporum canis (3 isolates), Epidermophyton floccosum (2 isolates), Candida albicans (32 isolates), Malassezia furfur (7 isolates) and Sporothrix schenckii (12 isolates). The results are summarized as follows: 1. MIC values of ITZ for the isolates of dermatophytes and M. furfur distributed in a range of less than 0.0012-5 micrograms/ml indicating that ITZ had greater in vitro activities. These in vitro activities of ITZ were greater than those of clotrimazole or bifonazole. 2. C. albicans isolates were divided into 2 groups in terms of ITZ-susceptibilities, a high susceptibility group and low-susceptibility group with MIC values of 0.02-0.08 micrograms/ml and greater than 10 micrograms/ml, respectively. 3. The in vitro activities of ITZ against S. schenckii isolates with a geometric mean MIC of 0.119 micrograms/ml were greater than those of ketoconazole, miconazole or amphotericin B used as reference drugs.     

Indian Medicinal Plants: A Potential Source for Anticandidal Drugs

Alcoholic and aqueous crude extracts of 37 traditionally-used medicinal plants were screened for antifungal activity against the pathogenic yeast, Candida albicans, and dermatophytes, Epidermophyton floccosum, Microsporum gypseum and Trichophyton rubrum. Alcoholic extracts of these 37 plants were demonstrated to have antifungal activity. Twenty-one extracts showed strong activity and the remaining 16 plants exhibited moderate activity against Candida albicans and to one or more dermatophytes. Such activity was detected in only 16 aqueous extracts. Alcoholic extracts of five medicinal plants were selected for further studies on the basis of their strong anticandidal activity. Minimum inhibitory concentration (MIC) values of these five extracts revealed their varied anticandidal potency. MIC values ranged between 4-9 mg/ml. Comparatively high potency was observed in the extracts of Plumbago zeylanica (4mg/ml) followed by Terminalia bellirica and Phyllanthus emblica (7 mg/ml), each Holarrhena antidysentrica (8 mg/ml), and least in Terminalia chebula (9 mg/ml). Preliminary phytochemical analysis of these extracts showed the presence of many biologically active constituents.     

Design, synthesis and antifungal activity of some new imidazole and triazole derivatives

Triazole and imidazole are incorporated into the structures of many antifungal compounds. In this study a novel series of 1,2,4-triazole, imidazole, benzoimidazole, and benzotriazole derivatives was designed as inhibitors of cytochrome P450 14α-demethylase (14DM). These structures were docked into the active site of MT-CYP51, using Autodock program. Sixteen compounds with the best binding energy were synthesized. The chemical structures of the new compounds were confirmed by elemental and spectral ((1) H-NMR and Mass) analyses. All compounds were investigated for antifungal activity against Candida albicans, Candida tropicalis, Candida glabrata, Candida parapeilosis, Candida kruzei, Candida dubliniensis, Aspergillus fomigatus, Aspergillus flavus, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophyte, Epidermophyton floccosum. Some compounds showed excellent in-vitro antifungal activity against most of the tested fungi. Compounds 2, 9, and 10 had antifungal activity against several resistant fungi against fluconazole and itraconazole.     

(E)-1-芳基-2-咪唑乙酮和(E)-1-芳基-2-苯并咪唑乙酮取代苯腙衍生物的合成及其抗真菌活性

根据抗真菌药物的作用机理和构效关系,本文设计合成了61个(E)-1-芳基-2-咪唑乙酮和(E)-1-芳基-2-苯并咪唑乙酮取代苯腙衍生物,其中57个化合物是未知的。初步抑菌试验结果表明,大多数化合物对深部致病真菌具有不同程度的抑菌作用。当苯环上有2,6-Cl₂,2,4-Cl₂,p-Cl,p-NO₂,p-OCH₃,p-SCH₃取代时,抗真菌活性较强,特别是有p-OCH₃取代的化合物(如:13,29,45)抗真菌活性优于或相似于克霉唑,抗菌谱也较广。     

N-(6,6-二甲基-2-庚烯-4-炔基)-N-甲基-α-取代-1-(4-取代)萘甲胺类的合成及抗真菌活性

根据氮唑类和烯丙胺类抗真菌化合物的构效关系、作用机理。设计合成了30个N-(6,6-二甲基-2-庚烯-4-炔基)-N-甲基-α-取代-1-(4-取代)萘甲胺类化合物。初步体外抑菌试验结果表明,大多数目标化合物对八种试验菌株都有不同程度的抗真菌活性。化合物Ⅰ_1a的真菌活性大致与克霉唑相当,对白念珠菌的活性明显高于naftifine和terbinafine,但对其它七种菌株的活性均不及naftifine和terbinafine;化合物Ⅲ_1a对八种试验菌株的活性均与terbinafine相当。