Synthesis and antimicrobial activity of new 2-[p-substituted-benzyl]-5-[substituted-carbonylamino]benzoxazoles

A series of 23 new 2-[p-substituted-benzyl]-5-[p-substituted-phenyl/benzyl-carbonylamino]benzoxazole derivatives has been synthesized by reacting 5-amino-2-[p-substituted-benzyl]benzoxazoles with the appropriate carboxylic acid chlorides. The structures of the synthesized compounds were confirmed by IR and (1)H-NMR spectral data. Antimicrobial activities of the compounds were investigated using the twofold serial dilution technique against two gram-positive and two gram-negative bacteria and three Candida species in comparison with standard drugs. Microbiological results indicated that the newly synthesized 2-[p-substituted-benzyl]-5-[p-substituted-phenyl/benzyl-carbonylamino]benzoxazole derivatives (3-25) possessed a broad spectrum of activity, showing MIC values of 6.25-200 microg/mL against the gram-positive and gram-negative microorganisms tested. Moreover, they showed significant antifungal activity with MIC values of 3.12-100 microg/mL against the Candida species tested. Especially, with a MIC value of 3.12 microg/mL, 2-benzyl-5-[p-bromobenzyl-carbonylamino]benzoxazole 9 displayed the same activity against C. glabrata as the standard drug myconazol.     

Synthesis, structure investigations, and antimicrobial activity of selected s-trans-6-aryl-4-isopropyl-2-[2-[(E)-1-phenylalkylidene]-(E)-hydrazino]-1,4-dihydropyrimidine hydrochlorides.

A series of 6-aryl-4-isopropyl-2-[2-(1-phenylalkylidene)hydrazino]-1,4-dihydropyrimidine hydrochlorides was prepared and tested for antibacterial and antifungal effects. The title compounds were synthesized by cyclocondensation of N(2)-(1-phenylalkylideneamino)guanidines with 1-aryl-4-methyl-2-penten-1-ones. Structure analyses of the prepared compounds were accomplished by means of 1D and 2D NMR spectroscopy. The analyses showed that the ring closure reaction took place regioselectively in all cases and generated exclusively 2-(phenylalkylidenehydrazino)dihydropyrimidines. According to the NOE experiments, the applied N(2)-(1-phenylalkylideneamino)guanidines exist in [D(6)]DMSO solution as s-trans-(E)- and the title compounds as s-trans-(E,E)-isomers. The antimicrobial activity was evaluated against representative Gram-negative and Gram-positive bacteria, and against the pathogenic yeast Candida albicans. The tested title compounds showed weak antibacterial activity against Gram-positive bacteria, and one compound was active against Candida albicans.     

N~2-芳基三嗪青霉素和N~2-苯基-N~4-烷基(芳基)三嗪青霉素的合成及其抗菌活性

设计合成了十个N~2-芳基三嗪青霉素和六个N~2-苯基-N~4-烷基(芳基)三嗪青霉素,这十六个化合物均为未见文献报道的新化合物,元素分析数据和光谱数据证实了它们的结构。初步体外抑菌试验表明,十六个化合物对G( )菌和G(-)菌均有一定的活性,其中的五个化合物具有一定程度的广谱特征。     

2-呋喃硫羰基腙衍生物及其过渡金属配位化合物的合成和抑菌活性

本文设计合成了九个2-呋喃硫羰基腙衍生物及其十三个不同的过渡金属配位化合物,并进行了抑菌实验,表明化合物对受试各种细菌均具有不同程度的抑菌作用。与2-呋喃硫羰基踪衍生物相比,配位化合物的抑菌活性发生显著的改变。其中,铜(Ⅱ)、镍(Ⅱ)、锌(Ⅱ)和银(Ⅰ)等配位化合物的活性较强,其它过渡金属配位化合物的活性较低。多数化合物对革兰氏阳性细菌的敏感性大于对革兰氏阴性细菌。     

Synthesis of some 1.3.4-thiadiazoles of possible antimicrobial activity

Different new esters of 5-aryl-1,3,4-thiadiazol-2-ylcarbazic acid and dithiocarbazic acid were prepared. In addition, the synthesis of 2-(N,N'-dialkylcarboxy)hydrazino-5-aryl-1,3,4-thiadiazoles is described. IR and NMR data of the new compounds are discussed. Some of these compounds showed a reasonable activity against Gram positive bacteria and fungi.     

Synthesis and antimicrobial activities of some new tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives of cefadroxil.

Eleven new 7-[2-(dihydro-5-substituted-6-thioxo-2H-1,3,5-thiadiazine-3( 4H)-yl)-2- (4-hydroxyphenyl)acetamido]-3-methyl-3-cephem-4-carboxylic acid derivatives were synthesized by the reaction of cefadroxil monohydrate, formaldehyde and substituted potassium dithiocarbamate. Their structures have been elucidated by spectral data and elementary analysis. The title compounds were tested for antimicrobial activity in vitro against gram-positive bacteria (Staphylococcus aureus, Streptococcus faecalis), gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and yeast-like fungi (Candida albicans, C. parapsilosis, C. stellatoidea, C. pseudotropicalis) in comparison with cefadroxil monohydrate. The activity of compounds 1 and 10 against S. aureus (MBC: 37.5 micrograms/ml) and compound 1 against E. coli (MBC: 75 micrograms/ml) were found to be the same as cefadroxil monohydrate. Compounds 1 and 10 were more effective than cefadroxil monohydrate against S. faecalis with 25 and 37.5 micrograms/ml MBC values, respectively. None of the compounds and cefadroxil monohydrate proved to be effective against P. aeruginosa (MBC: greater than 100 micrograms/ml). While cefadroxil monohydrate had no activity against yeast-like fungi, compounds 9 and 10 were significantly effective against yeast-like fungi (MFC: 37.5 micrograms/ml).     

N2-芳基三嗪青霉素和N2-苯基-N4-烷基(芳基)三嗪青霉素的合成及其抗菌活性

设计合成了十个N²-芳基三嗪青霉素和六个N²-苯基-N⁴-烷基(芳基)三嗪青霉素,这十六个化合物均为未见文献报道的新化合物,元素分析数据和光谱数据证实了它们的结构。初步体外抑菌试验表明,十六个化合物对G(+)菌和G(-)菌均有一定的活性,其中的五个化合物具有一定程度的广谱特征。     

四氢－2H－1，3，5－噻二嗪－2－硫酮类化合物的合成与抗菌活性

报道１０个四氢－２Ｈ－１，３，５－噻二嗪－２－硫酮类化合物的合成与体外抗菌试验，其中７个化合物为新化合物。经元素分析、紫外光谱、红外光谱及核磁共振氢谱等确证它们的结构，并试验它们对６种细菌和２种霉菌的生物活性。结果显示此类化合物的抗菌活性显著强于临床上正在使用的磺胺嘧啶钠注射液，而稍弱于诺氟沙星注射液。对革兰氏阴性菌的抑制作用强于对革兰氏阳性菌的作用，对霉菌的活性很弱。     

四氢-2H-1,3,5-噻二嗪-2-硫酮类化合物的合成与抗菌活性

报道10个四氢-2H-1,3,5-噻二嗪-2-硫酮类化合物的合成与体外抗菌试验,其中7个化合物为新化合物。经元素分析、紫外光谱、红外光谱及核磁共振氢谱等确证它们的结构,并试验它们对6种细菌和2种霉菌的生物活性。结果显示此类化合物的抗菌活性显著强于临床上正在使用的磺胺嘧啶钠注射液,而稍弱于诺氟沙星注射液。对革兰氏阴性菌的抑制作用强于对革兰氏阳性菌的作用,对霉菌的活性很弱。     

Synthesis and antimicrobial activity of 5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)thiazolidine-2,4-diones

A series of 5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)thiazolidine-2,4-diones was synthesized by Knoevenagel condensation of various 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehydes (1a–h) with thiazolidine-2,4-dione (2) in ethanol in the presence of piperidine. All compounds were screened for their in vitro antibacterial (Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli) activity and compared with the commercially available antibiotic, ciprofloxacin. All compounds showed good activity against gram-positive bacteria, however, none of the compounds were found to be effective against gram-negative bacteria. Compound 3g was found to be most potent member among all the compounds showing MIC of 16?μg/ml against S. aureus and 32?μg/ml against B. subtilis. All the synthesized compounds were also tested for their in vitro antifungal (Aspergillus niger and A. flavus) activity and compared with commercially available fluconazole. They showed excellent antifungal activity. Compounds 3b, 3e, 3f and 3g were active against both fungi showing more than 60% inhibition. Compound 3e was found to be superior to the reference drug.     

Synthesis, antimicrobial, and antiviral activities of some new 5-sulphonamido-8-hydroxyquinoline derivatives

A series of fused pyranopyrazole and pyranoimidazole, namely 5-(3,6-diamino-4-aryl-5-carbonitrile-pyrano(2,3-c)pyrazol-2-yl)sulphonyl-8-hydroxyquinolines (5a-e), 5-(6-amino-4-aryl-5-carbonitrile-pyrano(2,3-c)pyrazol-3-yl)sulphonamido-8-hydroxyquinolines (6a-e), 5-(2-thioxo-4-aryl-5-carbonitrile-6-amino-pyrano(2,3-d)imidazol-2-yl)sulphonyl-8-hydroxyquinolines (10a-e), and 5-(2-oxo-4-aryl-5-carbonitrile-6-amino-pyrano(2,3-d)imidazol-2-yl) sulphonyl-8-hydroxyquinolines (11a-e), have been prepared via condensation of some arylidine malononitriles with 5-sulphonamido-8-hydroxyquinoline derivatives 3, 4, 8 and 9. All the synthesized compounds were screened for their antimicrobial activities, and most of the tested compounds showed potent inhibition growth activity towards Escherichia coli, Pseudomonas aeruginosa (Gramnegative bacteria). Furthermore, six selected compounds were tested for their antiviral activity against avian paramyxovirus type1 (APMV-1) and laryngotracheitis virus (LTV), and the results showed that a concentration range of 3-4 μg per mL of compounds 2, 3, and 4 showed marked viral inhibitory activity for APMV-1 of 5000 tissue culture infected dose fifty (TCID(50)) and LTV of 500 TCID(50) in Vero cell cultures based on their cytopathic effect. Chicken embryo experiments show that compounds 2, 3, and 4 possess high antiviral activity in vitro with an inhibitory concentration fifty (IC(50)) range of 3-4 μg per egg against avian APMV-1 and LTV and their toxic concentration fifty (CC(50)) of 200-300 μg per egg.     

alpha-(1H-imidazol-1-ylmethylene)ketones with antimycotic activity

A series of title compounds were synthesized starting from heterocyclic alpha-hydroxymethyleneketones and 1,1'-carbonyldiimidazole and tested against gram-positive and gram-negative bacteria, as well as fungi. 7,8-Dihydro-6-(1H-imidazol-1-ylmethylene)-2-phenylquinazolin -5(6H)-one showed a remarkable activity against Candida krusei.     

Synthesis and microbiological activity of some novel N-[2-(p-substitutedphenyl)-5-benzoxazolyl]-cyclohexyl carboxamide, -cyclohexyl acetamide and -cyclohexyl propionamide derivatives

The synthesis and microbiological activity of a new series of N-[2-(p-substitutedphenyl)-5-benzoxazolyl]-cyclohexyl carboxamide, -cyclohexyl acetamide and -cyclohexyl propionamide derivatives (4-11) is described. The in vitro microbiological activity of the compounds was determined against gram-positive, gram-negative bacteria and the yeast Candida albicans in comparison with standard drugs. Microbiological results indicated that the synthesized compounds possessed a broad spectrum of activity against the tested microorganisms.     

Synthesis and antihypertensive activity of 1-(2-thiazolyl)-3, 5-disubstituted -2-pyrazolines

Several substituted 3-aryl-1-(4-aryl-2-thiazolyl)-5-(3-pyridyl)-2-pyrazolines were synthesized by reacting substituted 3-aryl-5-(3-pyridyl)-1-thiocarbamoyl-2-pyrazolines with phenacyl bromide in ethanol. The structures of all compounds were confirmed by IR, (1)H-NMR, mass spectral data and elemental analyses. The antihypertensive activity of compounds was examined by the tail-cuff method and compared with clonidine. Compounds 24-28 showed significant antihypertensive activity.     

2, 3-Bis(5-alkyl-2-thiono-1, 3, 5-thiadiazin-3-yl) propionic acid: one-pot domino synthesis and antimicrobial activity

In a search for promising antibacterial and antifungal compounds, two new series of 2, 3-bis(5-alkyl-2-thiono-1, 3, 5-thiadiazin-3-yl)propionic acid 1 and their corresponding N, N-dimethylpropionamide 6 have been synthesized. The reaction of 2, 3-diaminopropionate 3, carbon disulfide, formaldehyde, and the appropriate alkyl amines furnished the title compound 1. N, N-dimethylpropionamides 6 were obtained by the reaction of 1 with dimethyl amine in the presence of POCl(3). The newly prepared compounds were screened in vitro against certain strains of Gram-positive and Gram-negative bacteria and compared with nalidixic acid and ciprofloxacin. Moreover, the title compounds were tested for their antifungal activity in vitro against Candida albicans, phytopathogenic, Penicillum expansum and Trichoderma hazianum, and aflatoxin-producing Aspergillus flavus. These compounds exhibit varied activity against the tested pathogenic bacteria and remarkable inhibitory effects on growth or sporulation of some of the tested fungal species.     

Synthesis and evaluation of analgesic/ anti-inflammatory and antimicrobial activities of 3-substituted- 1,2,4-triazole-5-thiones

In this study, the synthesis of a novel series of Mannich bases of 5-mercapto-3-aryl-1,2,4-triazoles is described. The structures attributed to compounds la-5e were elucidated using IR and 1H-NMR spectroscopic techniques besides elemental analysis. The formation of 1-aminomethyl-3-substituted-1,2,4-triazole-5-thiones - not the isomeric 3-substituted-4-aminomethyl-1,2,4-triazole-5-thiones was unambiguously confirmed by X-ray crystallographic analysis of 1c. The compounds were examined for their in vivo anti-inflammatory and analgesic activity in two different bioassays, namely carrageenan-induced hind paw edema and p-benzoquinone-induced abdominal constriction tests in mice, respectively. In addition, the ulcerogenic effects of the compounds were determined. Among the tested derivatives most promising results were obtained for the compounds bearing a nonsubstituted phenyl group at C-3 position of the triazole ring (1a-e). The compounds were also evaluated for their in vitro antimicrobial activity against a series of gram positive bacteria [Staphylococcus aureus (ATCC 29213), Enterococcus faecalis (ATCC 29212)], gram negative bacteria [Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853)] and yeast-like microorganisms [Candida albicans (ATCC 90028), C. krusei (ATCC 6258), C. parapsilosis (ATCC 22019)]. One series of the examined compounds (3a-e) exhibited better antibacterial activity especially against gram positive bacteria than against gram negative bacteria. Compounds 2c, 3b, and 3e were found to be more effective against C. parapsilosis compared with the other derivatives (MIC: 16 microg/mL).     

Synthesis and antimicrobial activities of some new tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives of amoxicillin

A number of 6-[2-(dihydro-5-substituted-6-thioxo-2H-1,3,5-thiadiazine-3( 4H)-yl)-2-(4-hydroxyphenyl)acetamido]penicillanic acids has been synthesized as prodrugs by incorporating the amine group of amoxicillin trihydrate into tetrahydro-2H-1,3,5-thiadiazine-2-thione ring. The compounds have been prepared by the reaction of various alkyl or aralkyl amines with potassium hydroxide, carbon disulfide, formaldehyde and amoxicillin trihydrate. The structures of the compounds have been elucidated by UV, IR, 1H-NMR spectra and elementary analysis. The in vitro activity of these compounds against gram-positive bacteria (Staphylococcus aureus, Streptococcus faecalis), gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and yeast-like fungi (Candida albicans, C. parapsilosis, C. stellatoidea, C. pseudotropicalis) was investigated by the tube dilution method and compared with the activity of amoxicillin trihydrate. By this way their minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and minimal fungicidal concentration (MFC) values were determined. Compound I and Compound VII were significantly more effective than amoxicillin trihydrate against S. aureus (MBC: 6.25 micrograms/ml). Compound VI and Compound XI were effective against S. faecalis (MBC: 6.25 micrograms/ml) and Compound I and Compound VI were effective against E. coli (MBC: 12.5 micrograms/ml). All of the compounds and amoxicillin trihydrate were ineffective against P. aeruginosa (MIC: greater than 100 micrograms/ml). Compound IX and Compound X were the most active derivatives against yeast-like fungi; the MFC values for these compounds ranged between 6.25 and 37.5 micrograms/ml.     

(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。     

Synthesis of 2-mercaptobenzimidazole derivatives as potential anti-microbial and cytotoxic agents

A series of novel 2-(1H-benzimidazol-2-ylsulfanyl)-N-(4-oxo-2-phenyl-thiazolidin-3yl)-acetamide 5a-j have been synthesized from various aldehydes and 2-(5-phenyl-[1,3,4]-oxadiazol-2-ylmethylsulfanyl)-1H-benzimidazole 6a-j from various benzoic acids. These compounds were screened for their in-vitro anti-bacterial activity against Staphylococcus aureus and Enterococcus faecalis as Gram positive, Klebsiella pneumoniae and Escherichia coli as Gram negative bacterial strains and for in-vitro anti-fungal activity against Asperigillus fumigatus and Candida albicans. The in vitro cytotoxic properties were studied using brine shrimp bioassay. Results revealed that, compounds 5b, 5d, 5g, 5i, 6b, 6e, 6f, and 6i showed excellent activity against a panel of microorganisms. The cytotoxic activities of 5b, 5g, 5i, 6b, 6f, 6h, and 6i were found to be good. All the newly synthesized compounds were characterized by elemental analysis, IR, (1)H-NMR, (13)C-NMR and MS.     

Studies on FK482 (Cefdinir). III. Synthesis and structure-activity relationships of 7 beta-[(Z)-2-aryl-2-hydroxyiminoacetamido]-3-vinyl-3- cephem-4-carboxylic acid derivatives

The synthesis, antibacterial activity and oral absorption of the 7 beta-[(Z)-2-aryl-2-hydroxyiminoacetamido]-3-vinylcephalosporins (Ia--e) are described. All of these compounds exhibited excellent activity against Staphylococcus aureus. Against Gram-negative bacteria FK482 exhibited more excellent activity than the other compounds (Ia--e). These compounds except Ie showed good oral absorption. The relationship between the oral absorption rates and the lipophilicity of these cephalosporins is discussed.