Synthesis and antimicrobial activity of some 5-[2-(morpholin-4-yl)acetamido] and/or 5-[2-(4-substituted piperazin-1-yl)acetamido]-2-(p-substituted phenyl)benzoxazoles

In this study, a series of twelve novel 5-[2-(morpholin-4-yl)acetamido] and/or 5-[2-(4-substituted pip-erazine-1-yl)acetamido]-2-(p-substituted phenyl]benzoxazole derivatives have been synthesized and their structures were confirmed by IR, (1)H NMR, and mass spectral data. These compounds were prepared by reacting 5-(2-chloroacetamido)-2-(4-p-substituted-phenyl)benzoxazoles, which were obtained by using 5-amino-2-[p-substituted-phenyl]benzoxazoles with chloroacetyl chloride, in the presence of morpholine or 1-substituted piperazines. All synthesized compounds 3-14 were tested by using the method of twofold serial dilution technique for in vitro activities against certain strains of Gram-positive, Gram-negative bacteria as well as the yeasts Candida albicans, Candida krusei, and Candida glabrata in comparison with standard drugs. Microbiological results showed that the newly synthesized compounds possessed a broad spectrum of activity, showing MIC values of 3.12-50 mug/mL against the Candida species.     

Synthesis and antifungal activity of (+/-)-1-(5-aryl-3-pyridin-2-yl-4,5-dihydro-pyrazol-1-yl)-2-imidazol-1-yl-ethanone derivatives

(+/-)-1-(5-Aryl-3-pyridin-2-yl-4,5-dihydro-pyrazol-1-yl)-2-imidazol-1-yl-ethanone derivatives were synthesized and tested for their in vitro antifungal activity. The compounds showed a moderate activity against strains of Candida parapsilosis, Candida pseudotropicalis and Candida glabrata.     

Synthesis and biological activity of ethyl 2-(substituted benzylthio)-4-(3'-(ethoxycarbonyl)biphenyl-4-yl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate derivatives

In the present study, a new series of ethyl 2-(substituted benzylthio)-4-(3'-(ethoxycarbonyl)-biphenyl-4-yl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate derivatives was synthesized. The newly synthesized compounds were characterized by (1) H-NMR, mass and C, H, N analyses. All newly synthesized compounds were screened for their antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes and Klebsiella pneumoniae) and antifungal (Aspergillus flavus, Aspergillus fumigatus, Candida albicans, Penicillium marneffei and Trichophyton mentagrophytes) activity. The results revealed that all synthesized compounds have a significant biological activity against the tested microorganisms. Compounds 8a, 8b, 8c, 8e, 8f, 8i, and 8j exhibited good antimicrobial activity.     

Synthesis, characterization, and pharmacological evaluation of 1-[2-(6-nitro-4-oxo-2-phenyl-4H-quinazolin-3-yl)-ethyl]-3-phenyl ureas

In the present communication, a series based on 1-[2-(6-nitro-4-oxo-2-phenyl-4H-quinazolin-3-yl)-ethyl]-3-phenyl-urea have been synthesized by an efficient synthetic protocol. The synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR spectroscopy, ESI Mass spectrometry, and elemental analysis. The antibacterial and antifungal activity of the compounds were studied against selected strains (Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Bacillus subtilis ATCC 11774, and Candida albicans ATCC 66027) by using Kirby Bauer disk diffusion technique and broth dilution technique. All the synthesized compounds showed good antifungal potency against strain C. albicans.     

Synthesis and antileukemic activity of novel 2-(4-(2,4-dimethoxybenzoyl)phenoxy)-1-(4-(3-(piperidin-4-yl)propyl)piperidin-1-yl)ethanone derivatives

A series of novel 2-(4-(2,4-dimethoxybenzoyl)phenoxy)-1-(4-(3-(piperidin-4-yl)propyl) piperidin-1-yl)ethanone derivatives 9(a-e) and 10(a-g) were synthesized and characterized by (1) H NMR, IR, mass spectral, and elemental analysis. These novel compounds were evaluated for their antileukemic activity against two human leukemic cell lines (K562 and CEM) by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. Some of the tested compounds showed good antiproliferative activity with IC(50) values ranging from 1.6 to 8.0 μm. Compound 9c, 9e, and 10f with an electron-withdrawing halogen substituent at the para position on the phenyl ring showed excellent in vitro potency against tested human leukemia cells (K562 and CEM).     

1-(1H-1,2,4-三唑-1-基)-(2,4-二氟苯基)-3-取代-2-丙醇类化合物的合成及其抗真菌活性

目的研究不同取代哌啶和环仲胺侧链的引入对三唑醇类化合物抗真菌活性的影响。方法以氟康唑为先导化合物,设计合成了9个三唑醇类新化合物,化合物的结构均通过核磁、红外光谱确证;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。结果目标化合物对8种真菌特别是深部真菌均有一定的抑制作用,其中化合物4、5对白色念珠菌的MIC80值小于或等于0.125μg.mL-1,是氟康唑活性的4倍以上,与伊曲康唑活性相当。结论立体化学因素的改变对该类化合物体外抑菌活性有较大影响。     

1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物的合成及抗真菌活性

根据氮唑类抗真菌化合物的构效关系和作用机理,设计合成了29个1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物,其中九个为首次报道。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14对白念珠菌的活性与克霉唑及益康唑相当,对其它七种试验菌株的活性明显强于克霉唑及益康唑。化合物4,12对白念珠菌活性差,对其它七种试验菌株的活性也强于克霉唑和益康唑。化合物5,6和23除对白念珠菌外,对其它七种试验菌株,也有较强活性。     

1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物的合成及抗真菌活性

根据氮唑类抗真菌化合物的构效关系和作用机理,设计合成了29个1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物,其中九个为首次报道。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14对白念珠菌的活性与克霉唑及益康唑相当,对其它七种试验菌株的活性明显强于克霉唑及益康唑。化合物4,12对白念珠菌活性差,对其它七种试验菌株的活性也强于克霉唑和益康唑。化合物5,6和23除对白念珠菌外,对其它七种试验菌株,也有较强活性。     

Synthesis and antimicrobial properties of 3-aryl-1-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-yl)propanes as 'carba-analogues' of the N-arylmethyl-N-[(1,1'-biphenyl)-4-ylmethyl])-1H-imidazol-1-amines,a new class of antifungal agents

A new series of 3-phenyl-1-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-yl)propane derivatives 2a-l (related to the antifungal bifonazole) was synthesized and tested for antimicrobial activity. A number of substituents on the phenyl ring were chosen to compare the relative biological properties with those of corresponding aza-analogues, previously described by us. The in vitro antifungal activities of the newly synthesized azoles were tested against several pathogenic fungi responsible for human disease. Test pathogens included representatives of yeasts (Candida albicans, Candida parapsilosis, Criptococcus neoformans), dermathophytes (Tricophyton verrucosum, Tricophyton rubrum, Microsporum gypseum) and moulds (Aspergillus fumigatus). Bifonazole and miconazole were used as reference drugs. Title compounds were prepared by alkylation of 1-biphenyl-4-yl-2-imidazol-1-yl-ethanone with the proper arylmethyl halide and subsequent reduction of corresponding ketones applying the Huang-Minlon modification of the Wolff-Kishner reaction.     

Synthesis, antibacterial and antifungal activity of some novel 3-[5-(4-substituted phenyl) 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones

A series of novel 3-[5-substituted phenyl-1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones were synthesized and evaluated for antibacterial activity against pathogenic strains of Staphylococcus aureus (MTCC no. 96), Bacillus subtilis (MTCC no. 619), Pseudomonas aeruginosa (MTCC no. 424) and Escherichia coli (MTCC no. 40) and antifungal activity against Aspergillus niger, Candida albicans and Fusarium oxysporum. The cup-plate method was employed to determine the minimum inhibitory concentration (MIC) value of the compounds. Some of the compounds exhibited activity comparable to Norfloxacin. The present report reveals that synthesized 2-styryl-quinazoline-4(3H)-one exhibited better antibacterial than antifungal activity.     

1-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-3-取代-2-丙醇的合成及抗真菌活性研究

１（１Ｈ１，２，４三唑１基）２（２，４二氟苯基）３取代２丙醇的合成及抗真菌活性研究张大志周廷森吴义杰刘超美麻铭川冯向庭（第二军医大学药学院，上海２００４３３）氮唑类化合物是目前抗真菌药物研究最为活跃的领域之一。该类化合物可分...     

1-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-3-[(4-取代)-哌嗪-1-基]-2-丙醇的合成及其抗真菌活性

目的研究不同取代哌嗪侧链的引入对三唑醇类化合物抗真菌活性的影响.方法设计合成了13个三唑醇类新化合物;选择8种真菌为实验菌株,进行体外抑菌活性测试.结果目标化合物对8种真菌特别是深部真菌均有一定的抑制活性,其中有8个化合物对白色念珠菌的MIC80值小于或等于0.125μg/mL,是氟康唑活性的4倍以上,与酮康唑活性相当.结论脂水分配系数和立体化学因素的改变对该类化合物体外抑菌活性有较大影响.     

Synthesis and antifungal activity of 1-[(2-benzyloxy)phenyl]-2-(azol-1-yl)ethanone derivatives: exploring the scaffold flexibility

Based on the N-(phenethyl)azole backbone of azole antifungals, we designed 1-[(2-benzyloxy)phenyl]-2-(azol-1-yl)ethanone derivatives 2 and 3, containing benzyloxyphenyl scaffold of croconazole. Also these compounds can be considered as flexible analogs, resulted from C2-C3 disconnection of 3'-chloro-3-imidazolylflavanone 1, recently described as antifungal agent. Thus, in this report, we describe the synthesis of 1-[(2-benzyloxy)phenyl]-2-(azol-1-yl)ethanone derivatives 2 and 3 and their biological evaluation against different pathogenic fungi. By comparing the antifungal activity profile of flexible compounds 2 and 3 with that of rigid analog 1, it can be inferred that lower susceptibilities (higher minimum inhibitory concentrations) were observed with flexible compounds. However, among the synthesized compounds, 1-[2-(2,4-dichlorobenzyloxy)phenyl]-2-(1H-imidazol-1-yl)ethanone hydrochloride (2g) showed comparable or more potent antifungal activity in comparison with fluconazole as a standard drug.     

叔丁基三唑衍生物的合成及抗真菌活性研究

目的研究具有叔丁基结构的三唑醇类化合物的抗真菌活性以及各种4-(4-烷氧基苯基)哌嗪侧链的引入对抗真菌活性的影响.方法以一氯频那酮、三氮唑为原料,经多步反应合成目标化合物,化合物结构经IR、1H-NMR谱确证;选择8种真菌为实验菌株,按国际标准抗真菌敏感性实验方法测定其体外抗真菌活性.结果设计合成了10个新化合物.10个目标化合物对8种真菌均具有一定的抑制活性,其中,有4个化合物对白色念珠菌的MIC80值小于或等于0.125 mg·L-1,是氟康唑的4倍以上,与伊曲康唑相当.结论可以通过引入更多的疏水基团设计三唑醇类化合物,立体化学因素对该类化合物的体外抑菌活性有较大影响.     

Synthesis, antimicrobial activity, and molecular modeling of novel 4-(3-(4-benzylpiperazin-1-yl)propoxy)-7-methoxy-3-substituted phenyl-2H-chromen-2-one

A series of novel 4-(3-(4-benzylpiperazin-1-yl)propoxy)-7-methoxy-3-substituted phenyl-2H-chromen-2-one (7a–7j) were synthesized by the reductive amination of 7-methoxy-3-phenyl-4-(3-piperizin-1-yl-propaxy)chromen-2-one (6) with different substituted aromatic aldehydes by using sodium cyanoborohydride in methanol. The newly synthesized compounds were purified and their structures were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectroscopy. The representative analogs were screened for in vitro antimicrobial activity. The compounds exhibited significant antibacterial and antifungal activity as that of standards. The data was further compared with structure-based investigations using docking studies with the crystal structure of oxidoreductase (1XDQ and 3QLS) protein organisms. The estimated score by genetic algorithm was found to have a good correlation with the experimental inhibitory potency of the derivatives.     

New 6-Bromo-2-Methyl-3-(Substituted Phenyl)-(3H)-Quinazolin-4-Ones with Antimicrobial and Antiinflammatory Activities

New quinazolin-4-one derivatives, 6-bromo-2-methyl-3-(substituted phenyl)-(3H)-quinazolin-4-one, were synthesized and evaluated for antimicrobial and antiinflammatory activities. The structures attributed to synthesized compounds 1-8 were supported by the results of elemental analysis as well as by the UV, IR and (1)H NMR spectral data. Investigation of antimicrobial activity was performed using cup-plate agar diffusion method against Bacillus subtilis, Staphylococcus aureus and Pseudomonas aeruginosa and Candida albicans, Aspergillus niger and Curvularia lunata. Antiinflammatory activity was evaluated using the carrageenan-induced paw oedema test in rats. The results showed that compounds 2b, 2c, 2d, 2g and 2h exhibited significant antibacterial and antifungal activity comparable to standard drugs and compounds 2b and 2c showed good antiinflammatory activity comparable to ibuprofen.     

7-{4-［2-［2-取代-4-((5S)-5-乙酰胺甲基-2-氧代-噁唑烷-3-基)苯基］乙基］哌嗪-1-基}-氟喹诺酮类化合物的合成与抗菌活性

目的寻找新型的噁唑烷酮-氟喹诺酮类抗菌药物。方法设计合成了7-{4-［2-［2-取代-4-((5S)-5-乙酰胺甲基-2-氧代-噁唑烷-3-基)苯基］乙基］哌嗪-1-基}-氟喹诺酮类化合物，测定其体外抗菌活性。结果共合成20个目标化合物，经^{1H NMR和MS确证结构。目标化合物具有较好的体外抗菌活性，尤其是化合物22，对屎肠球菌的抑制活性分别是吗啉噁酮和诺氟沙星的16倍和64倍，对金葡菌的抑制活性为吗啉噁酮的4倍。结论某些带有氟喹诺酮结构片段的噁唑烷酮类化合物抗菌活性加强。}     

Synthesis of promising antimicrobial agents: a novel series of N-(4-(2,6-dichloroquinolin-3-yl)-6-(aryl)pyrimidin-2-yl)-2-morpholinoacetamides

A series of novel compounds N-(4-(2,6-dichloroquinolin-3-yl)-6-(aryl)pyrimidin-2-yl)-2-morpholinoacetamides (5a–l) were synthesized by a series of multistep reactions. Newly synthesized compounds have been characterized by IR, ¹H NMR, ¹³C NMR, and mass spectral data. Antimicrobial screening of title compounds 5a–l was examined against Gram-positive bacteria (Staphylococcus aureus and Streptococcus pyogenes), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and three fungi (Candida albicans, Aspergillus niger, and Aspergillus clavatus) by serial broth dilution method. Synthesized compounds showed potent inhibitory action against test organisms. Screened compounds 5e–g and 5i–l were associated with considerably higher antibacterial and antifungal activities than commercially used antibiotics.     

Antibacterial, antifungal and anticonvulsant evaluation of novel newly synthesized 1-[2-(1H-tetrazol-5-yl)ethyl]-1H-benzo[d][1,2,3]triazoles

Several novel 1-[2-(1H-tetrazol-5-yl) ethyl]-1H-benzo[d][1,2,3]triazoles (3a-h) have been synthesized by the condensation of 1-[2-(1H-tetrazol-5-yl)-ethyl]-1H-benzotriazole (2) and appropriate acid chlorides. 1-[2-(1H-tetrazol-5-yl)-ethyl]-1H-benzotriazole (2) was synthesized by reacting 3-(1H-benzo[d][1,2,3]triazol-1-yl)propanenitrile with sodium azide and ammonium chloride in the presence of dimethylformamide. The synthesized compounds were characterized by IR and PMR analysis. The titled compounds were evaluated for their in-vitro antibacterial and antifungal activity by the cup plate method and anticonvulsant activity evaluated by the maximal electroshock induced convulsion method in mice. All synthesized compounds exhibited moderate antibacterial activity against Bacillus subtilis and moderate antifungal activity against Candida albicans. Compounds 5-(2-(1H-benzo[d][1,2,3]triazo-1-yl)ethyl)-1H-tetrazol-1-yl)(4-aminophenyl)methanone 3d and 5-(2-(1 H-benzo[d][1,2,3]triazo-1-yl)ethyl)-1H-tetrazol-1-yl)(2-aminophenyl)methanone 3e elicited excellent anticonvulsant activity.     

N-〔3-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-2-羟基-丙基〕-氨基乙酸及其衍生物的合成和抗真菌活性

设计合成了Ｎ〔３（１Ｈ１，２，４三唑１基）２（２，４二氟苯基）２羟基丙基〕氨基乙酸及其９个衍生物，均为未见文献报道的新化合物，初步药理试验表明：部分化合物对浅部真菌有一定的活性，除卡氏枝孢霉菌外，对其它深部真菌活性较弱，其中化合物（５ｅ），（５ｈ）对某些真菌的体外活性较强，明显优于氟康唑，但稍弱于酮康唑