Antibacterial activities of cefotiam against various pathogens isolated from clinical materials (author's transl)

Bacteriological evaluation was made on cefotiam (CTM), a new broad-spectrum cephalosporin antibiotic, and the following results wer obtained. 1) CTM has shown very potent antibacterial activities against Staphylococcus aureus, Escherichia coli, Edwardsiella tarda, Citrobacter intermedius, Salmonella, Klebsiella, Proteus mirabilis, Proteus rettgeri, Proteus inconstans, Yersinia enterocolitica, Aeromonas hydrophila, Plesiomonas shigelloides and Pseudomonas putrefaciens. 2) Streptococcus faecalis, Enterobacter and Proteus morganii isolated from urine, Serratia and glucose non fermentative Gram-negative bacilli except Pseudomonas putrefaciens, were almost insusceptible to cefotiam.     

Synthesis and antifungal activities of N-arylideneaminoimidazole derivatives

The synthesis and microbiological activities of 1-arylideneaminoimidazole derivatives are reported. Antimicrobial data show that some of the tested imidazoles exhibited an interesting activity on Candida albicans.     

四氢异喹啉衍生物的合成及抗真菌活性

目的 寻找新的抗真菌活性化合物。方法 采用Pictet-Spengler法合成四氢异喹啉，再通过氮直接烃化法合成目标化合物，并对目标化合物进行初步的体外抗真菌活性实验。结果 合成了18个新的四氢异喹啉衍生物，利用红外光谱、核磁共振谱进行了结构确认。结论 所合成的18个四氢异喹啉衍生物具有不同程度的抗真菌活性。     

In vitro and in vivo antifungal activities of the eight steroid saponins from Tribulus terrestris L. with potent activity against fluconazole-resistant fungal pathogens

Antifungal activity of natural products is being studied widely. Saponins are known to be antifungal and antibacterial. We have isolated eight steroid saponins from Tribulus terrestris L., namely TTS-8, TTS-9, TTS-10, TTS-11, TTS-12, TTS-13, TTS-14 and TTS-15. TTS-12 and TTS-15 were identified as tigogenin-3-O-beta-D-xylopyranosyl(1-->2)-[beta-D-xylopyranosyl(1-->3)]-beta-D-glucopyranosyl(1-->4)-[alpha-L-rhamnopyranosyl(1-->2)]-beta-D-galactopyranoside and tigogenin-3-O-beta-D-glucopyranosyl(1-->2)-[beta-D-xylopyranosyl(1-->3)]-beta-D-glucopyranosyl(1-->4)-beta-D-galactopyranoside, respectively. The in vitro antifungal activities of the eight saponins against six fluconazole-resistant yeasts, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, Candida krusei, and Cryptococcus neoformans were studied using microbroth dilution assay. The results showed that TTS-12 and TTS-15 were very effective against several pathogenic candidal species and C. neoformans in vitro. It is noteworthy that TTS-12 and TTS-15 were very active against fluconazole-resistant C. albicans (MIC(80)=4.4, 9.4 microg/ml), C. neoformans (MIC(80)=10.7, 18.7 microg/ml) and inherently resistant C. krusei (MIC(80)=8.8, 18.4 microg/ml). So in vivo activity of TTS-12 in a vaginal infection model with fluconazole-resistant C. albicans was studied in particular. Our studies revealed TTS-12 also showed in vivo activities against fluconazole-resistant yeasts. In conclusion, steroid saponins TTS-12 and TTS-15 from Tribulus terrestris L. have significant in vitro antifungal activity against fluconazole-resistant fungi, especially TTS-12 also showed in vivo activity against fluconazole-resistant C. albicans.     

新型三唑类衍生物的合成及其抗真菌活性研究

目的：研究具有萘苄结构的三唑醇类化合物的抗真菌活性。方法设计合成了9个目标化合物;其结构通过1 H NMR、MS确证,选择8种真菌为实验菌株,根据美国国家临床实验室标准委员会（NCCLS）推荐的标准化抗真菌敏感性实验方法,进行体外抑菌活性测试。结果所有化合物对所选真菌均表现出了一定的抑菌活性,化合物1c对除烟曲霉菌以外的其他7种真菌的MIC80值＜0．125μg/ml,是伏立康唑活性的16倍。结论引入萘环和烃基侧链的目标化合物都有抗真菌活性。     

新型三唑类衍生物的合成及抗真菌活性研究

目的:研究具有萘苄结构的三唑类化合物的抗真菌活性.方法:设计合成了10个三唑类新化合物,其结构通过1H-NMR、MS确证,选择8种真菌为实验菌株,进行体外抑菌活性测试.结果:所有化合物对所选真菌均表现出了一定的抑菌活性,部分化合物对白念珠菌的MIC80值＜0.125μg/ml,是伏立康唑活性的16倍.结论:引入萘环和烷基侧链的目标化合物都具有抗真菌活性.     

188株血液培养阳性病人病原菌分布及耐药分析

目的 研究2016年上半年入该院血液培养阳性病人病原菌分布和耐药情况,为临床用药提供科学依据.方法 收集2016年1月1日-2016年6月30日入院病人血培养,阳性者进行细菌培养和鉴定,用Whonet5.6软件耐药情况分析.结果2016上半年总共有1 760例病人做血液培养,188例培养阳性,阳性率是10.68%,革兰阴性杆菌102株,占54.26%,大肠埃希菌(57株)、鲍曼不动杆菌(8株)和铜绿假单胞菌(8株);革兰阳性球菌74株,占39.36%,表皮葡萄球菌(23株)、金黄色葡萄球菌(20株)和粪肠球菌(12株);真菌12株,占6.38%.大肠埃希菌对美平和亚胺培南耐药率为0.表皮葡萄球菌、金黄色葡萄球菌对糖肽类抗生素(万古霉素、替考拉宁和利奈唑胺)的耐药率均为0,未发现耐万古霉素的葡萄球菌.结论 2016上半年该院血培养阳性最多的菌株是大肠埃希菌,对血培养阳性结果进行细菌培养和药敏鉴定,为临床诊断治疗用药提供科学依据.     

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.     

Antibacterial, antifungal and cytotoxic activities of amblyone isolated from Amorphophallus campanulatus

Objective:

To assess the in vitro antibacterial, antifungal and cytotoxic activities of amblyone, a triterpenoid isolated from Amorphophallus campanulatus (Roxb).

Methods:

Disc diffusion technique was used for in vitro antibacterial and antifungal screening. Cytotoxicity was determined against brine shrimp nauplii. In addition, minimum inhibitory concentration (MIC) was determined using serial dilution technique to determine the antibacterial potency.

Results:

Large zones of inhibition were observed in disc diffusion antibacterial screening against four Gram-positive bacteria (Bacillus subtilis, Bacillus megaterium, Staphylococcus aureus and Streptococcus pyogenes) and six Gram-negative bacteria (Escherichia coli, Shigella dysenteriae, Shigella sonnei, Shigella flexneri, Pseudomonas aeruginosa and Salmonella typhi). The MIC values against these bacteria ranged from 8 to 64 μg/ml. In antifungal screening, the compound showed small zones of inhibition against Aspergillus flavus, Aspergillus niger and Rhizopus aryzae. Candida albicans was resistant against the compound. In the cytotoxicity determination, LC₅₀ of the compound against brine shrimp nauplii was 13.25 μg/ml.

Conclusions:

These results suggest that the compound has good antibacterial activity against the tested bacteria, moderate cytotoxicity against brine shrimp nauplii and insignificant antifungal activity against the tested fungi.     

维康芬净及其衍生物的抗真菌活性研究

维康芬净(aherfungin)是一种新型β-1,3-葡聚糖合成酶抑制剂,由一株高产紫杉醇菌种发酵产生,结构上是枝孢菌素(cladosporol)的手性异构体.本研究在于阐明维康芬净及其衍生物的抗真菌活性及其药用价值.采用琼脂块稀释法和液体稀释法,以氟康唑为对照,经多次重复实验.测得维康芬净及其衍生物的MIC在0.2～128μg/ml之间,其中以维康芬净的抗菌活性较强,且抗菌谱较广.     

Antibacterial,antifungal and cytotoxic activities of salviasperanol isolated from Amorphophallus campanulatus

Salviasperanol, a diterpenoid isolated from Amorphophallus campanulatus (Roxb.) Bl. (Araceae) was studied for in vitro antibacterial, antifungal, and cytotoxic activities. The disc diffusion technique was used to determine in vitro antibacterial and antifungal activities. Cytotoxicity was determined against brine shrimp nauplii. In addition, minimal inhibitory concentration (MIC) was determined using serial dilution technique to determine antibacterial potency. The MIC values against these bacteria ranged from 8 to 64 μg/mL. The compound showed significant antibacterial activity against four Gram-positive bacteria (Bacillus subtilis, Bacillus megaterium, Staphylococcus aureus, Streptococcus β-haemolyticus) and six Gram-negative bacteria (Escherichia coli, Shigella dysenteriae, Shigella sonnei, Shigella flexneri, Pseudomonus aeruginosa, Salmonella typhi). The compound showed weak antifungal activity against a number of fungi. In the cytotoxicity determination, the LC₅₀ of the compound against brine shrimp nauplii was 8.02 μg/mL.     

Synthesis, antibacterial and antifungal activities of bifonazole derivatives

Two series of chlorinated benzhydryl imidazole and triazole derivatives were synthesized and tested in vitro against representative strains of potent pathogenic bacteria (Staphylococcus aureus CIP 4.83, Escherichia hirae CIP 5855, Pseudomonas aeruginosa CIP 82118, Escherichia coli CIP 53126) and fungi (Aspergillus niger IP 1431.83, Candida albicans IP 48.72, Candida krusei IP 208.52, Trichophython rubrum IP 1657.86). Most of these compounds were devoid of any antimicrobial activity, but several of them inhibited T. rubrum with MIC values in the range of 0.125 to 32 μg/mL, similar or superior to those of bifonazole and clotrimazole, used as standard controls. The replacement of the imidazole ring with a triazole moiety in these compounds led to derivatives with less antifungal activity. A preliminary SAR was undertaken on the effect of the number and the position of chlorine atoms on the distribution of negative charge on the surface of some compounds on antifungal activity.     

Synthesis and antifungal activities of novel 2-aminotetralin derivatives

Novel 2-aminotetralin derivatives were synthesized as antifungal agents. The 2-aminotetralin scaffold was chemically designed to mimic the tetrahydroisoquinoline ring of the lead molecule described before. Their antifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 10a, 12a, 12c, 13b, and 13d are more potent than fluconazole against seven testing human fungal pathogens. Compound 10b exhibits much higher antifungal activities against all of the four fluconazole-resistant clinic Candida albicans strains than the control drugs including amphotericin B, terbinafine, ketoconazole, and itraconazole. The mode of action of some compounds to the potential receptor lanosterol 14alpha-demethylase (CYP51) was investigated by molecular docking. The studies presented here provide a new structural type for the development of novel antifungal compounds. Furthermore, 10b was evaluated in vivo by a rat vaginal candidiasis model, and it was found that 10b significantly decreases the number of fungal colony counts.     

没食子酰哌嗪类化合物的合成及抗真菌作用研究

目的 设计合成没食子酰哌嗪衍生物,考察其对耐药真菌的抗菌活性。方法 以三甲氧基没食子酸为原料,在PyBOP/DIEA存在下与哌嗪反应得到中间体,在脱保护后与相应的酸缩合,最后脱甲基得到目标化合物。采用美国国家临床实验室标准委员会（CLSI）推荐方法,将目标化合物对2株临床分离的耐药白色念珠菌株进行体外抗真菌活性试验,进而与氟康唑（8 μg/ml）联用,开展协同抗真菌活性试验。结果 共合成了11个化合物,其中6个化合物表现出优于没食子酸的抗真菌活性。结论 没食子酰哌嗪可以提高没食子酸的抗真菌活性,没食子酸酰结构是重要的药效团,若引入桂皮酸或2,3-二氯苯甲酸可以进一步提高活性。     

Trypanocidal and antifungal activities of p-hydroxyacetophenone derivatives from Calea uniflora (Heliantheae, Asteraceae)

The dichloromethane extract of underground parts of Calea uniflora (Heliantheae, Asteraceae) exhibited trypanocidal and antifungal activities. Four p-hydroxyacetophenone derivatives were isolated as the main compounds: 2-senecioyl-4-(hydroxyethyl)-phenol (1), 2-senecioyl-4-(angeloyloxy-ethyl)-phenol (2), and two new derivatives, 2-senecioyl-4-(methoxyethyl)-phenol (3) and 2-senecioyl-4-(pentadecanoyloxyethyl)-phenol (4). 1 and 4 were active towards Trypanosoma cruzi trypomastigotes, reducing their number by 70 and 71% at 500 microg x mL(-1), whereas 2 and 3 were inactive. All the compounds tested showed antifungal activity with minimal inhibitory concentration values between 500 and 1000 microg x mL(-1) against pathogenic Candida spp. and dermatophytes. The isolation, structure elucidation, NMR spectral assignments and bioactivity results of these compounds are reported.     

温莪术内生真菌对植物病原真菌抑菌活性的研究

目的 研究温莪术内生真菌对植物病原真菌的抑制作用.方法 以玉米大斑病菌胁Helm inthos porium turcic-um、黄瓜枯萎病菌Fusarium oxysporium f.sp.cilium ennum、禾谷镰孢菌Fusarium graminearum、立枯丝核菌Rhizoctonia solani、串珠镰孢菌Fusarium moniliforme和玉米弯孢叶斑病菌Curvularia lunata为供试菌种,对55株温莪术Curcuma aromatica Salisb内生真菌及其次生代谢物进行抑菌活性的试验.结果 有15株内生菌及19株次生代谢产物至少对3种测试菌有抑制作用,9株内生菌及11株次生代谢产物对6种测试菌有抑制作用.结论 从温莪术内生真菌中可以选择出对植物病原真菌具有良好抑制作用的菌种.     

含硫的三唑类化合物的合成及抗真菌活性研究

目的设计合成含有二硫代甲酸酯侧链的新型三氮唑类化合物,并研究其体外抗真菌活性。方法通过与二硫化碳的加成及取代反应合成了9个新型三氮唑类化合物,其结构通过1 H NMR和MS确证,并选择8种真菌为实验菌株,对其体外抗真菌活性进行测试。结果所有化合物对实验菌株均有一定的抗菌活性,尤其对白色念珠菌活性较好,化合物6d对白假丝酵母菌的MIC80值<0.125μg/ml,是伊曲康唑的64倍。结论引入丙基、硫元素和取代苄基侧链对目标化合物的抗真菌活性影响较大;二硫代甲酸酯结构的引入有利于提高三唑类化合物的体外抗真菌活性。     

Synthesis and antibacterial and antifungal activities of thiourea derivatives of the alkaloid anabasine

A series of new N-acyl-substituted derivatives of the physiologically active alkaloid anabasine were synthesized and described. Their compositions and structures were identified using IR and ¹H NMR spectroscopy. These compounds were found to have moderate antibacterial and antifungal activities.