Synthesis of Pyridazinonethiadiazoles as Possible Antifungal Agents

Several 5-[1-aryl-1,4-dihydro-6-methylpyridazin-4-one-3-yl]-2-arylamino-1,3,4-thia diazoles were synthesized. The preliminary bio-active test shows that these compounds exhibit high antifungal activity.

Synthesis of a New Series of Chalcone Derivatives and Their Antifungal Activities

To study the antifungal effect of chalcone derivatives. Methods Sixteenchalcone derivatives were synthesized and confirmed by ~1H NMR and IR spectra, and tested forantifungal activity against four common pathogenic fungi. Their structure-activity relationship isdiscussed. Results Among 16 title compounds, there were 5 new compounds, which have not beenreported before. The preliminary antifungal test showed that all title compounds exhibitedantifungal activities to a certain extent. The activity of compound 8 against Trichophyton rubrumhad a potency equal to that of fluconazole, with a MIC of 4 μg·mL^(-1) . Conclusion Sixteenchalcones were prepared and their antifungal activities against four common pathogenic fungi invitro were examined. Some of them exhibited antifungal activities to a certain extent.

Topical Treatment of Infectious Vaginitis:Effects of Antibiotic,Antifungal and Antiseptic Drugs on the Growth of Normal Vaginal Lactobacillus Strains

Objectives: The balance of the vaginal ecosystem depends on lactobacilli whose biofilm protectsagainst microorganisms that are not normally present or are subdominant in vaginal flora. Vaginal?infection treatments should eliminate pathogens while preserving the?Lactobacillus?flora to prevent relapse or recurrence. The objective of this study was to determine the sensitivity of lactobacilli to antiseptics, antibiotics and antifungal agents used, alone or in combination, in the topical treatment of infectious vaginitis. Materials and Methods: The minimum inhibitory concentration (MIC) of 15 active ingredients and the minimum inhibitory dilution (MID) of 17 pharmaceuticals products were determined for three main?Lactobacillus?strains (L. crispatus,?L. gasseri?and?L. jensenii). Results: The MICs of the antibiotics and antifungal agents were above their critical concentrations in the three strains, contrary to the antiseptics. According to their MID, some pharmaceutical products, especially combinations, inhibit the growth of one or more strains at concentrations that can be found in the vaginal mucosa after application at the usual dosage. Conclusions: Certain topical anti-infective drugs may interfere with the growth of lactobacilli, worsening the vaginal flora imbalance. Maintaining vaginal flora balance should be a selection criterion when choosing an anti-infective therapy.

Antifungal Evaluation of Copper(Ⅱ) Complex from a Schiff Base Derivative of Pyrazine on Schizosaccharomyces pombe

A new copper(Ⅱ) complex of CuLCl_2, where L = N^1-(1-pyrazin-2-yl-ethylidene)-ethane-1,2-diamine, a tridentate Schiff base derived from 2-acetylpyrazine has been prepared. The complex has been characterized by FT-IR, elemental analysis and single-crystal X-ray diffraction studies. Structural studies reveal that CuLCl_2 is a mononuclear copper(Ⅱ) complex with distorted square pyramidal geometry. Antifungal activity of CuLCl_2 was investigated by use of microcalorimetric measurement system and evaluated against S. pombe. It has high antifungal activity with IC_(50) = 213 μg/mL.

Antifungal Susceptibility Testing of Dermatophytes by ABDD and E-Test, a Comparative Study

Aim: The objective of this study was to isolate, identify, and explore the in-vitro antifungal susceptibility pattern of dermatophytes isolated from clinically suspected cases of dermatophytosis (tinea infections) attending the Dermatology Department at J.S.S Hospital. Methods: This study was conducted at JSS Medical College and Hospital from December 2016 to December 2017. Clinical samples (e.g., skin scrapings and hair stumps) were collected under aseptic precautions. The identification of dermatophytes was performed through microscopic examination using 10%, 20% & 40% potassium hydroxide (KOH) and culture on Sabouraud dextrose agar (SDA), SDAac, PDA and Dermatophyte test medium (DTM). All dermatophytes isolates were subjected to antifungal susceptibility testing using the agar-based disk diffusion (ABDD) and E-test method against Terbinafine, Itraconazole, Fluconazole, and Griseofulvin. Data were analyzed by using Chi square test. Results: A 100 samples were studied, 46% tinea corporis, 2%tinea cruris, 9% tinea pedis, 5% tinea faciei. The dermatophytes isolated were Trichophyton rubrum 11 (35%), Trichophyton mentagrophyte 8 (25%), Trichophyton tonsurans 5 (16%), Microsporum gypseum 3 (10%), Trichophyton verrucosum 2 (6%), Trichophyton violaceum 1 (3%) and Microsporum audouinii 1 (3%). Out of 31 dermatophytes 17 were sensitive to all four antifungal agents within the range of FLC (2 - 6 mcg/ml), ITR (0.125 - 2), TER (0.125 - 2), and GRI (0.125 - 2), 5 isolates were resistant in which 2 were resistant to FLC (64.256 mcg/ml), 2 isolates were resistant to TER 2 (32.38 mcg/ml), 1 isolate was resistant to both GRI and TER (16.32 mcg/ml) and 9 isolates were within the intermediate range. Conclusion: Every patient with a tinea infection should be properly studied for a mycological examination and should be treated accordingly. Dermatophyte test medium is more useful as an identification medium in the isolation of dermatophytes. The ABDD method appears to be a simple, cost-effective, and promising method for the evaluation of antifungal susceptibility of dermatophytes. E-test method is the most sensitive method due to the fact that quantitative MICs can be obtained directly from the E-strip. However, the E-test method is expensive and difficult in defining the precise borders of the inhibition zones in dermatophytes.

2018—2022年华东地区临床分离念珠菌耐药性监测

目的监测中国华东地区临床分离念珠菌的耐药性,为临床诊断和治疗提供参考。方法以质谱或分子的方法对2018年1月—2022年12月收集的菌株进行复核鉴定,采用肉汤微量稀释法进行10种抗真菌药物的药敏试验。依据2022年美国临床和实验室标准化协会(CLSI)M27 M44s-Ed3和M57s-Ed4对药敏试验结果进行判读。结果共收集念珠菌3026株,无菌部位分离菌株占65.33%,主要标本类型为血液38.86%和胸腹水10.21%。白念珠菌占比(44.51%)最高、其次为近平滑念珠菌复合群19.46%、热带念珠菌13.98%、光滑念珠菌10.34%和其他念珠菌0.79%。对测试的10种抗真菌药物:白念珠菌较为敏感,敏感率最低为93.62%,2.97%的菌株对氟康唑剂量依赖性敏感(SDD);近平滑念珠菌对氟康唑SDD为2.61%,耐药率为9.42%,对其他药物的敏感率均大于90%;光滑念珠菌对氟康唑SDD为92.01%,耐药率为7.99%,泊沙康唑、伏立康唑非野生型菌株(NWT)分别为32.27%、48.24%,其他药物的敏感率均大于90%;热带念珠菌对氟康唑、伏立康唑耐药率分别为29.55%、26.24%,对泊沙康唑、伊曲康唑NWT分别为76.60%、21.99%,对棘白菌素类药物耐药率为2.36%。结论华东地区念珠菌的分离率和菌种分布与国内外报道基本一致,近平滑念珠菌复合群对氟康唑有一定的耐药性,热带念珠菌对三唑类药物有较高的耐药性,光滑念珠菌对氟康唑非敏感率较高。白念珠菌、近平滑念珠菌、热带念珠菌和光滑念珠菌均出现了对棘白菌素类耐药菌株。

南通市蚕豆赤斑病病原菌鉴定及其抑菌药剂筛选

为明确江苏省南通市蚕豆赤斑病的病原菌种类,对致病菌进行分离纯化,并结合致病性测定、形态学观察和多基因碱基序列分析对疑似病原菌进行鉴定。结果表明,南通市蚕豆赤斑病病原菌为拟蚕豆葡萄孢(Botrytis fabiopsis)。生物学特性分析结果表明,该病原菌菌丝的最适生长温度为25℃,最适光照条件为12 h光照+12 h黑暗,对pH不敏感,最适碳源为葡萄糖,最适氮源为酵母膏、牛肉膏和硫酸铵,最适培养基为马铃薯葡萄糖琼脂(PDA)培养基。抑菌药剂筛选结果表明,2.0%苦参碱水剂和10.0%苯醚甲环唑水分散粒剂对病原菌的抑制效果最好,半数效应浓度(EC_(50))分别为0.0054 mg/L和0.7554 mg/L,而10.0%多抗霉素可湿性粉剂和80.0%波尔多液可湿性粉剂对病原菌几乎无抑制效果。本研究结果可为江苏省南通市蚕豆赤斑病的科学防治提供理论基础。

金属纳米颗粒治疗白念珠菌感染研究进展

念珠菌病在全球范围内有很高的发病率及死亡率,其主要病原体是白念珠菌。目前,由于抗真菌药物存在毒性、耐药性、给药途径单一、价格昂贵等缺陷,使得念珠菌病治疗效果不理想。为了克服这一现状,具有抗真菌活性和运载抗真菌药物潜力的金属纳米颗粒被广泛研究。该文综述了金、银、铜、铁纳米颗粒的抗白念珠菌的作用机制及应用进展。与传统抗真菌药物比较,金属纳米颗粒通过多靶点机制发挥抗真菌作用,可最大限度地减少抗真菌耐药性的出现。虽然细胞毒性限制了金属纳米颗粒的应用,但绿色合成可降低金属纳米颗粒的细胞毒性并提高其抗菌性能等。

马尾松木材防霉防蓝变研究进展

马尾松(Pinus massoniana Lamb.)是我国南方分布最广,最主要的用材树种之一,生长速度快、适应能力强、木材力学性能好,被广泛应用于建筑、造纸、装饰、家具、交通等行业。然而,由于其内部含有许多营养物质,易受到霉菌和蓝变菌的侵害。本文重点对国内外传统和新型的马尾松木材防霉防蓝变药剂和处理方法进行了阐述,同时对存在的问题进行了分析,并对研究方向进行了展望,旨在为今后开发新型防霉防蓝变药剂和方法提供理论支持。

氯喹对白念珠菌生物膜及其耐药性的作用研究

目的探究氯喹单独使用及联用传统抗真菌药物对白念珠菌生物膜及其耐药性的改变。方法采用白念珠菌标准株及耐药株进行实验,使用XTT减低法和棋盘稀释法分别检测氯喹单独使用及联用抗真菌药物后对两种白念珠菌生物膜的抑制作用,绘制时间-杀菌曲线,扫描电镜观察两种白念珠菌生物膜形态。结果50μmol/L及以上浓度氯喹对两种白念珠菌生物膜有直接抑制作用,且随着浓度增加,抑制作用增强。氯喹与两性霉素B联用存在协同抑菌作用。氯喹单独使用和联用两性霉素B的时间-杀菌曲线结果显示,白念珠菌在不同时相培养中生长趋势有所不同;形态学观察发现均可降低白念珠菌菌丝和生物膜形成能力。结论氯喹对白念珠菌生物膜存在直接抑制,可降低白念珠菌生物膜耐药性。氯喹与两性霉素B联用时具有协同作用。

杭州市外耳道真菌病病原菌分布及药物敏感性分析

目的分析杭州市外耳道真菌病患者的临床特征、病原菌分布及药物敏感性,为外耳道真菌病的规范治疗提供帮助。方法收集2022年12月~2024年2月于浙江中医药大学附属第一医院诊治的115例鼓膜完整的外耳道真菌病患者耳部分泌物进行培养,通过形态学检查和质谱检测鉴定病原菌种类。采用真菌药敏板进行药敏实验。所有患者均在耳内镜下清理耳道联合局部注药。结果本地区外耳道真菌病常见致病菌以土曲霉为主(60.8%)。药敏结果可见土曲霉对泊沙康唑、伏立康唑和伊曲康唑均敏感,对其余6种药物存在不同程度耐药。纳入115例患者治疗总有效率达93%。结论本地区外耳道真菌病病原菌以土曲霉为主,其对泊沙康唑、伏立康唑和伊曲康唑等唑类抗真菌药物敏感,可作为临床治疗首选。

中国抗真菌药品应用现状及目录优化思考

我国侵袭性真菌感染的患病率逐年增加。然而,依据相关政策规定,医院采购抗真菌药品存在品种限制,临床目前用药品种的药理作用又相似度较高,可能导致对侵袭性真菌感染的治疗延迟。笔者总结了我国抗真菌药的适应证与临床应用现状,通过药品可及性分析,了解常见抗真菌药的药理特点及部分不可替代使用药品的局限性。基于此,认为相关部门应适当放宽抗真菌药品品种限制政策;医疗机构应定期(1~2年)调整、优化其供应目录与品种结构;同时,由于近年来国内外深部真菌病相关指南和专家共识中对伊曲康唑的推荐地位低,但在皮肤和黏膜等浅表真菌感染指南共识推荐地位较高,建议根据医疗机构真菌病病种的分布特征选择是否列入抗菌药品目录。

Assessing the Efficacy of Lemongrass (Cymbopogon citratus) and Sambong (Blumea balsamifera) Extracts in Combating Black Pod Disease: Sustainable Solutions for Controlling Phytophthora megakarya in Cameroon’s Cocoa Plantations

The use of plant extracts as antifungal agents is gaining increasing attention, particularly for the control of black pod disease in cocoa. Despite extensive research, current strategies haven’t been entirely effective. This study evaluated the effectiveness of Cymbopogon citratus and Blumea balsamifora leaf extracts, both individually and in combination, against Phytophthora megakarya. We assessed the efficacy of the most promising combination (75% B. balsamifera, 25% C. citratus) after storage at room temperature for up to 9 days. Agar microdilution and in vivo bioassays were conducted to determine antifungal susceptibility and effectiveness. Blumea extract exhibited the highest overall inhibitory activity, with the lowest minimum inhibitory concentration (117 µl mL−1) while C. citratus had a narrower range of MIC (146 to 233 µl mL−1). The combination of C. citratus and B. balsamifera demonstrated a synergistic effect against P. megakarya, achieving growth inhibition on V8 media (92.72 ± 4.20% to 100%) and on artificially infected detached pod cortex (92.24 ± 4.53% to 98.75 ± 1.25%), which was not significantly different from the positive control (Ridomil). Furthermore, this combination maintained its effectiveness for up to 9 days at room temperature. These findings suggest that combining plant extracts can enhance their antifungal properties.

Structure-Activity Relationship, Cytotoxicity and Mode of Action of 2-Ester-substituted 1,5-Benzothiazepines as Potent Antifungal Agents

Our studies examined the structural features responsible for the antifungal activity of 2-ethoxycarbonyl-1,5- benzothiazepine （7a）. Three series of 1,5-benzothiazepine derivatives were synthesized and screened for their antifungal activity. The results suggested that the ethoxycarbonyl group at the 2 position and the imine moiety on the seven-membered ring are essential for activity. The most potent of the synthesized analogues （7a, 7b） were further studied by evaluating their cytotoxicity and mode of action （for 7a）. The results showed that compounds 7a and 7b were relatively safe for BV2 cells, but compound 7a interfered with Cryptococcus neoformans cell wall integrity by increasing the chitinase activity. Therefore, compound 7a was considered safe as an antifungal agent for animal cells.

Graphene oxide-Fe_3O_4 nanocomposites as high-performance antifungal agents against Plasmopara viticola

Plasmopam viticola, a causal agent of grapevine downy mildew, is a widely distributed pathogen, which can cause destructive disease in field-grown grapevines. Although fungicides are used to treat the disease, fungicide-resistant strains have been emerging. In this study, we developed graphene oxide （GO）-Fe3O4 nanocomposites, which could effectively repress the germination of sporangia and inhibit the development of downy mildew. 50 μg mL^-1 GO-Fe3O4 showed excellent protective and fungiddal activities. 250 μg mL^-1 GO-Fe3O4 on grapevine leaves in the field could significantly decrease the severity of downy mildew, suggesting its potent curative effect. Moreover, GO-Fe3O4 had no significant toxic effects on grapevine plants even at the concentration twice that of the highest dosage （1000 μg mL^-1） used in this study. Our work suggested that GO-Fe3O4 would offer an important opportunity to develop new approach for controlling plant diseases.

Design,synthesis and biological evaluation of novel non-azole derivatives as potential antifungal agents

A series of 3-substituted quinazolinones,2-substituted quinoxalines and 2-substituted benzopyrans were synthesized and evaluated for their antifungal activity in vitro.The new compounds revealed excellent in vitro antifungal activity with broad spectrum.The structure-activity relationships（SARs） of the derivatives were analyzed.Compound 9A2 exhibits better antifungal activity against 5 tested fungi in vitro than fluconazole,especially against Trichophyton rubrum and Microsporum gypseum.This study provides a series of novel lead compounds for the development of non-azole antifungal agents.

In vitro activities of five antifungal agents against pathogenic Exophiala species

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卡泊芬净联合其他抗真菌药物治疗恶性血液病患者中性粒细胞缺乏合并侵袭性真菌感染的有效性和安全性探讨

目的探讨卡泊芬净联合其他抗真菌药物治疗恶性血液病患者中性粒细胞缺乏合并侵袭性真菌感染的有效性和安全性。方法60例恶性血液病中性粒细胞缺乏合并侵袭性真菌感染患者,采用卡泊芬净联合其他抗真菌药物治疗。分析患者的临床资料[基础疾病治疗方式、是否首选、感染部位、可疑感染部位病原菌(曲霉属)]、治疗效果、卡泊芬净不良反应发生情况及临床表现。结果60例患者中保守治疗10例,化疗及其他治疗50例;首选35例,其他药物治疗后换用25例;肺部感染32例,其他部位感染28例;感染部位病原菌(曲霉属)阳性38例,阴性22例。60例患者治疗显效50例,显效率为83.33%。60例患者中29例发生不良反应,不良反应发生率为48.33%(29/60),其中消化系统不良反应6例,代谢和营养异常7例,泌尿系统不良反应6例,输液反应5例,皮肤不良反应5例。患者不良反应程度比较轻,经有效治疗后,均有好转。结论采用卡泊芬净联合其他抗真菌药物对恶性血液病患者中性粒细胞缺乏合并侵袭性真菌感染进行治疗,有效性和安全性比较高,可推广。

用于上浆整理的4种防霉剂性能比较及其应用

为解决织物在织造和存放时发霉的问题,选用活性组分分别为碘丙炔基正丁胺甲酸酯(IPBC)、吡啶硫酮锌(ZPT)、辛基异噻唑啉酮(OIT)、氯化银(AgCl)的4种防霉剂,以产黄青霉和杂色曲霉为试验菌种,通过最小杀菌浓度(MBC)试验对比防霉剂的抑菌性能。结果表明:AgCl的MBC值最小,即杀菌能力最强,其次是IPBC和OIT,ZPT的最大。将上述4种防霉剂添加到3种常见的浆料(丙烯酸酯类、聚乙烯醇类、淀粉类)中,抑菌圈、浆料黏度和Zeta电位(ζ)等测试结果证明:浆料性质是影响防霉剂扩散的主要因素;其中,OIT与3种浆料的配伍性最好,市场应用价值最高。最后,通过上浆整理的方法将防霉剂应用到织物上,对整理织物的表面形貌、接触角、防霉等级等进行分析,结果表明:通过浸轧上浆处理,防霉剂可以均匀附着在织物表面使织物获得防霉能力;浆料的黏度和亲疏水性对上浆整理后织物的防霉性能影响显著。研究结果可为防霉上浆整理的工程应用提供参考。