咪唑并［2,1-b］［1,3,4］噻二唑及杂环氨曼尼希碱盐酸盐的合成及抗菌活性

为了进一步优化由噻二唑核稠合的水溶性稠杂环化合物的合成方法及抗菌活性，本文用2-(4-甲氧苯基)-5-氨基-1,3,4-噻二唑(2)与α-氯代-4-氯苯乙酮(3)缩合得6-(4-氯苯基)-2-(4-甲氧苯基)-咪唑并［2,1-b］［1,3,4］噻二唑(4)，4与取代哌嗪发生亲核取代反应得到6-(4-取代哌嗪-1-苯基)-2-(4-甲氧苯基)-咪唑并［2,1-b］-［1,3,4］噻二唑(5)，5与杂环氨进行曼尼希反应并与盐酸成盐得目标化合物6-(4-取代哌嗪-1-苯基)-2-(4-甲氧苯基)-5-杂环氨基甲基-咪唑并［2,1-b］［1,3,4］噻二唑盐酸盐(1)。用试管二倍稀释法评价了15个新化合物的体外抗菌活性，结果表明，随着极性基团的引入，抗菌活性显著提高，提示该类化合物的结构修饰值得进一步研究。     

Synthesis and antibacterial activity of N-[5-chlorobenzylthio-1,3,4-thiadiazol-2-yl] piperazinyl quinolone derivatives

A series ofN-[5-(chlorobenzylthio)-1,3,4-thiadiazol-2-yl] piperazinyl quinolone derivatives (4a-1) have been synthesized by reaction of piperazinyl quinolones with 5-chloro-2-(chloroben-zylthio)-1,3,4-thiadiazoles. Their structures were confirmed by elemental analysis, IR and NMR spectra. The antibacterial activities of4a-1 against a variety of Gram-positive and Gram-negative bacteria were determined. Several compounds showed a good antibacterial activity against Gram-positive bacteria among which, compound 4e with a 2-chlorobenzylthio moiety in ciprofloxacin derivative, exhibited high activities againstStaphylococcus aureus andStaphylococcus epidermidis (MIC=0.06 μg/mL). The structure-activity relationship (SAR) study revealed that the position of chlorine atom on benzyl moiety would dramatically affect the antibacterial activities of the synthesized compounds.     

磺胺取代2─氨基─1，3，4─噻二唑及其过渡金属配合物的合成及抑菌活性

合成了４种磺胺取代２－氨基－１，３，４－噻二唑配体及其８种与过渡金属（铜、钴）的配合物．配体结构由元素分析及红外光谱证实，配位情况依据原子吸收数据进行了计算与推断．对全部化合物进行了初步抑菌活性筛选，结果显示：钴配合物的抗菌活性较强     

Synthesis, structure and biological activity of novel 1,2,4-triazole mannich bases containing a substituted benzylpiperazine moiety

A series of novel Mannich bases with trifluoromethyl-1,2,4-triazole and substituted benzylpiperazine moieties were synthesized. Their structures were confirmed by IR, (1) H NMR and elemental analysis. The single crystal structure of compound 4r was also determined. The preliminary bioassays showed that most of the lead compounds had low herbicidal activity against Brassica campestris, Echinochloa crusgalli, and KARI enzyme. However, most of them exhibited significant fungicidal activity at the dosage of 50 μg/mL toward five test fungi. Among the 18 novel compounds, several showed superiority over the commercial fungicide Triadimefon against Cercospora arachidicola and Fusarium oxysporum f. sp. cucumerinum during this study. Meanwhile, some compounds displayed plant growth regulatory activity at the dosage of 10 μg/mL.     

Synthesis and Antimicrobial Activities of a Novel Series of Heterocyclic α‐Aminophosphonates

Two series of novel α‐aminophosphonates having heterocyclic moieties were synthesized in high yields. The structures of the newly synthesized compounds were confirmed by their elemental analyses, IR, ¹H NMR and MS spectral data. These compounds were screened for their antibacterial activities against Escherichia coli (NCIM2065) as a Gram‐negative bacterium, Bacillus subtilis (PC1219) and Staphylococcus aureus (ATCC25292) as Gram‐positive bacteria, and Candida albicans and Saccharomyces cerevisiae as fungi. The minimum inhibitory concentrations (MICs) of the synthesized compounds show high antibacterial and antifungal activities at low concentrations (10–1000 µg/mL). Furthermore, their lethal doses indicated that such compounds are safe for use as antimicrobial agents.     

3-(4-哌嗪-1-苯基)-6-取代-s-三唑并［3,4-b］［1,3,4］噻二唑盐酸盐的合成及抗菌活性

为了研究水溶性稠杂环化合物的合成方法及抗菌活性，本研究采用3-(4-氯苯基)-6-取代-s-三唑并［3,4-b］［1,3,4］噻二唑(2a～n)在相转移催化剂TBAI作用下与哌嗪发生亲核取代，再与盐酸成盐制备了3-(4-哌嗪-1-苯基)-6-取代-s-三唑［3,4-b］［1,3,4］噻二唑盐酸盐(3a～n)。用试管二倍稀释法研究了新化合物的体外抗菌活性。结果表明，合成的28个新化合物极性碱性哌嗪基的引入可提高化合物的抗菌活性。该类稠杂环化合物的结构有待进一步优化。     

Synthesis of 4-aminoantipyrine Schiff bases and their antimicrobial activities

Various compounds of 4-aminoantipyrine Schiff bases (M₁–M₁₂) were synthesized via a condensation reaction of 4-aminoantipyrine with different benzaldehydes through a conventional method of refluxing the mixture for 3–4 h. The synthesizedSchiff bases were characterized by using elemental analyses, FT-IR, UV-Vis, Mass, ¹H and ¹³C NMR spectroscopy. The antimicrobial activity of the synthesized Schiff bases was investigated against 12 bacterial strains(Mycobacterium smegmatis, Bacillus cereus, Bacillus subtilis, Enterococcus faecalis, Staphylococcus epidermidis, Klebsiella pneumonia, Escherichia coli, Enterobacter cloacae,Klebsiella oxytoca, Proteus vulgaris, Enterobacter aerogenes, and Pseudomonas aeruginosa), and antifungal activities were tested against seven fungal strains (Aspergillus flavus, Aspergillus carbonarious, Aspergillus parasiticus, Aspergillus fumigatus,Aspergillus niger, Fusarium verticillioides and Fusarium proliferatum). The antimicrobial activities of the synthesized compounds were compared with standard streptomycin and nalidixicacid. The results obtained from antibacterial assay indicated that M₁–M₁₂ inhibited potential growth of Proteus vulgaris with minimum inhibitory concentrations (MICs) ranging from 15.6–250 µg/mL compared with the standard nalidixic acid with an MIC of 500 µg/mL. Moreover, we could conclude that most of the tested compounds experienced mild to low activities at 15.6 µg/mL. Their activities could be attributed to their low concentrations.The antifungal analysis showed that the tested fungi were not sensitive to the prepared Schiff bases at the prepared concentration of 500 µg/mL. Therefore, we recommended further analysis on both cytotoxicity and minimum bactericidal concentration (MBC) to ascertain their potential effects against human cells.     

Design, Facile Synthesis, and Antibacterial Activity of Hybrid 1,3,4-thiadiazole-1,3,5-triazine Derivatives Tethered via -S- Bridge

Some hybrid 1,3,4-thiadiazole-1,3,5-triazine derivatives tethered via -S- bridge were synthesized and characterized with the aid of spectroscopic and elemental analysis. These hybrid conjugates were then investigated for their antibacterial activity against selected Gram-positive and Gram-negative bacteria. Excellent to moderate antibacterial activity was presented by the target compounds.     

The Antibacterial Activity of Compounds Isolated from Oakmoss against Legionella pneumophila and Other Legionella spp

Oakmoss is a natural fragrance ingredient exhibiting highly specific, potent antibacterial activity against Legionella pneumophila, a causative agent of severe water-bone pneumonia. In the present study, the antibacterial activity of individual compounds isolated from oakmoss was investigated against L. pneumophila and other Legionella spp. A total of 18 known compounds and two minor novel compounds (i.e., 3-methoxy-5-methylphenyl-2,4-dihydroxy-6-methylbenzoate (compound 9) and 8-(2,4-dihydroxy-6-(2-oxoheptyl)-phenoxy)-6-hydroxy-3-pentyl-1H-isochromen-1-one (compound 20)) were purified from oakmoss. The minimum inhibitory concentrations (MICs) against clinical and environmental isolates of L. pneumophila, L. bozemanii, L. micdadei, L. longbeachae, and L. dumoffii for 11 of the 20 compounds were less than 100?μg/mL (range 0.8-64.0?μg/mL). Novel compounds 9 and 20 exhibited potent antibacterial activity against L. pneumophila strains (MIC ranges of 1.3-8.0?μg/mL and 3.3-13.3?μg/mL, respectively) and also against four other Legionella species (MIC ranges of 0.8-8.0?μg/mL and 3.3-21.3?μg/mL, respectively). Time-kill assays indicated that compounds 9 and 20 kill bacteria at a concentration equivalent to 2×MIC after 1?h and 6?h co-incubations, respectively. While oakmoss and the purified components exhibited antibacterial activity against Legionella spp., they were not active against other Gram-negative and -positive bacteria such as Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus.     

Potential antimicrobial agents-I: Structural modifications and antimicrobial activity of some isatin derivatives

New isatin-3-isonicotinylhydrazones, isatinazine and its Mannich bases and spiro (indoline-3, 2'-thiadiazoline)-2-one have been synthesized. These compounds have been screened for their antibacterial activity against the Gram-positive and Gram-negative bacteria.     

N-取代苯基-5-取代苯基-3H-1,2,4-三唑-3-硫酮衍生物的合成及抗菌活性研究

目的 以苯甲酸为原料,经4步反应合成一系列N-取代苯基-5-取代苯基-3H-1,2,4-三氮唑-3-硫酮化合物并研究其抗菌活性。方法 基于课题组前期对新型潜在三唑类抗菌化合物6h的作用机制研究,筛选多个侧链基团,使用乙醇和碳酸钠作溶剂改善最后一步反应条件,通过硅胶柱色谱分离纯化目标化合物,合成一系列1,2,4-三唑类化合物并采用质谱(MS)和1H NMR、13C NMR进行结构表征。通过琼脂扩散法初步筛选所有化合物对肺炎克雷伯菌、金黄色葡萄球菌和铜绿假单胞菌3种常见菌株的抗菌活性,并通过微量稀释法进一步测定它们的最小抑菌浓度(MIC值)。结果 合成17个含有卤代苯基和其他侧链基团的目标化合物,其MS以及核磁共振谱图数据表明所有化合物结构正确。抗菌活性初步筛选可知化合物6a、6b、6d、6f、6g、6h、6k、6m和6p等9个化合物具有不错的抑菌能力,其MIC测试结果表明,大部分化合物对所测菌株的MIC值在25~100μg/mL范围内。尤其是化合物6h和6k对肺炎克雷伯菌的MIC值达到25μg/mL,抑菌活性与对照药物氨苄西林相当。结论 在前期作用机制研究基础上,通过对构效关系的阐述,发现一些侧链片段如间位卤代苯基或对位卤代苯基、三氟甲基苯基等具有吸电子基团的苯基、吡啶基等对1,2,4-三唑类衍生物的抗菌活性有明显增强作用,证实侧链基团与受体蛋白形成特异性协调作用和氢键作用从而发挥衍生物的抗菌活性。     

Design,synthesis, and in vitro antituberculosis activity of benzo[6,7]cyclohepta[1,2‐b]pyridine‐1,3,4‐oxadiazole derivatives

A new antitubercular agents, benzo[6,7]cyclohepta[1,2‐b]pyridine‐1,3,4‐ oxadiazole hybrids ( 6a–o ), have been designed and synthesized involving oxidative cyclization of hydrazones by use of di(acetoxy)iodobenzene, characterized by IR,¹H NMR,¹³C NMR, and HRMS, and further confirmed by X‐ray analysis. All the newly synthesized compounds 4a–o evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC27294). Among the compounds tested, the compounds 4o (MIC: 1.56  μg/ml) and 4l, 4m (MIC: 3.125  μg/ml) are promising lead analogues and have shown lower cytotoxicity.     

Synthesis and in vitro antibacterial activity of some N-(5-aryl-1,3,4-thiadiazole-2-yl)piperazinyl quinolone derivatives

A series of N-[5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole-2-yl] and N-[5-(nitrophenyl)-1,3,4-thiadiazole-2-yl] piperazinyl quinolone derivatives (5a-c and 5d-l) were synthesized and evaluated for in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria. The antibacterial data revealed that all nitroimidazole derivatives (5a-c) showed interesting activity against tested Gram-positive bacteria (minimum inhibitory concentration, MIC=0.008-0.03 microg/ml) while they did not show good activity against Gram-negative organisms. Despite the significant activity of nitroimidazole series, all nitrophenyl analogues (5d-l) were inactive against both Gram-positive and Gram-negative bacteria. Among all of the tested compounds, 5a (ciprofloxacin derivative in nitroimidazole series) exhibited excellent activity against Staphylococcus aureus and Staphylococcus epidermidis (MIC=0.008 microg/ml).     

Synthesis and biological evaluation of 1,2,4‐triazole‐3‐thione and 1,3,4‐oxadiazole‐2‐thione as antimycobacterial agents

Resistance among dormant mycobacteria leading to multidrug‐resistant and extremely drug‐resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4‐triazole‐3‐thione and 1,3,4‐oxadiazole‐2‐thione derivatives ( 4a–5c ) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC₅₀) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram‐negative and Gram‐positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100 μg/ml against THP‐1, A549, and PANC‐1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection.     

Synthesis and antibacterial activity of various substituted oxadiazole derivatives

Some new 2-(2-(4(4-substitutedbenzoyl-2-methylphenoxy)acetyl)-N-(2-substitutedphenyl) hydrazinecarbothioamides (4a-4j) and (4-((5-(2-substitutedphenylamino)-1,3,4-oxadiazol-2-yl)methoxy)-3-substitutedphenyl)(phenyl)methanones (5a-5j) have been synthesized from 2-(4-(3-substitutedbenzoyl)-2-methylphenoxy)acetohydrazides (3a, 3b). These newly synthesized compounds (4a-4j and 5a-5j) were characterized by elemental and spectral (IR, (1)H-NMR and MS) analysis. All the synthesized compounds have been screened for their antibacterial activity against both types of Gram negative and Gram positive bacteria. The most potent antibacterial compound of this series was compound 5i which has the low MIC 3.75-0.9375 μg/mL value. Both minimal inhibitory concentration (MIC) and inhibition zones were determined in order to monitor the efficacy of the synthesized compounds. Certain compounds inhibit bacterial growth with low MIC (μg/mL) value.     

Synthesis of some halogen-containing 1,2,4-triazolo-1,3,4-thiadiazines and their antibacterial and anticancer screening studies--part I

A series of 7-arylidene-6-(2,4-dichloro-5-fluorophenyl)-3-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (3) were prepared by the condensation of 4-amino-5-mercapto-3-substituted-1,2,4-triazoles (1) and 3-aryl-1-(2,4-dichloro-5-fluorophenyl)-2-bromo-2-propen-1-one (2). An alternative route for the synthesis of the title compound 3 has been described. The newly synthesised compounds were characterised on the basis of N-analyses, IR, 1H NMR and mass spectral data. Some of the newly synthesised compounds were tested for their antibacterial activities against Gram + ve and Gram - ve bacteria. Among the tested compounds 3n showed the highest degree of antibacterial activity against S. aureus and evaluation of the LD50 value of this compound was carried out. Some of the newly synthesised compounds were also screened for their anticancer activities. Among these, compounds 3b, 3g, 3n and 3p are found to be active against NCI-H460 (lung), MCF7 (breast), SF 268 (CNS) in the preliminary anticancer screening studies. Further, 60-cell-line anticancer studies of these compounds were carried out. The results of such studies are discussed in this paper.     

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.     

Towards eradicating antibiotic-resistant bacteria: synthesis and antibacterial activities of substituted N-(2-nitrophenyl)pyrrolidine- and piperidine-2-carboxylic acids

Antibacterial resistance is a source of great concern in the effective prevention and treatment of infections caused by bacteria, making the development of requisite therapeutics a major challenge. N-(Nitrophenyl)cycloamino acids are important compounds in the synthesis of poly-condensed nitrogen-containing heterocycles with marked activities in many biological systems. A series of substituted N-(o-nitrophenyl)cycloamino-2-carboxylic acids 3a–3g were synthesized via the condensation reaction of substituted o-halogenonitrobenzenes with L-proline 2a and D,L-pipecolinic acid 2b, under refluxing alcoholic basic conditions in excellent yields. The synthesized compounds were characterised by FT-IR, (¹H & ¹³C) NMR, UV-Vis, mass spectroscopy and elemental analysis. Their antibacterial activities were evaluated against five Gram-positive and five Gram-negative bacterial strains using the broth micro-dilution procedure. The antibacterial activities of the synthesized compounds were compared with streptomycin and nalidixic acid as standard antibiotic drugs. The minimum inhibitory concentration (MIC) values of compounds 3a–3g revealed good antibacterial activities against the tested microorganisms. Compounds 3a–3g were more potent than nalidixic acid against Enterococcus faecalis, Mycobacterium smegmatis, Escherichia coli and Proteus vulgaris and also more potent than streptomycin against Enterobacter cloacae and Staphylococcus aureus. Compounds 3a, 3c and 3g displayed the highest antibacterial potency with an MIC value of 15.6 μg/mL against E. cloacae, E. faecalis and P. mirabilis, respectively. These results indicated that these aryl cycloamino acids with antibacterial activities had potential applications as substitutes for antimicrobial peptide antibiotics, which are not susceptible to bacterial resistance, to solve the problem of drug resistance.     

Synthesis,antibacterial, antifungal and genotoxic activity of bis-1,3,4-oxadiazole derivatives

In the present investigation, four 1,3,4-bis-oxadiazole derivatives were synthesized as potential antimicrobial agents. The compounds are: 5,5'-dimercapto-bis-[1,3,4-oxadiazol-2-yl]propane (2a), 5,5'-dimercapto-bis-[1,3,4-oxadiazol-2-yl]butane (2b), 5,5'-dimercapto-bis-[1,3,4-oxadiazol-2-yl]octane (2c) and 5,5'-dibenzylthio-bis-[1,3,4-oxadiazol-2-yl]butane (3). The above newly synthesized compounds were investigated for their antibacterial, antifungal and mutagenic activities. The results of the biological activities revealed that the compounds 2a-c exhibited both antibacterial and antifungal activities against S. aureuss and B. subtilis. Compound 2a also showed activity against P. aeureoginosa. All the above compounds and compound 3 exhibited activity against C. albicans. Genotoxic studies showed that compound 2a had a weak base pair substitution mutagenicity but none of them exhibited a frameshift mutagenic action using Ames test.     

Novel 3‐Substituted Ocotillol‐Type Triterpenoid Derivatives as Antibacterial Candidates

Plant‐derived triterpenoid saponins are involved in the plant defense system by targeting bacterial membranes. A series of ocotillol‐type triterpenoid derivatives were synthesized starting from PPD, one of the main components of Panax ginseng and their antibacterial activity against several representative bacteria were evaluated. Compounds 5 and 11 exhibited excellent antibacterial activity with MIC values of 1 μg/mL against Staphylococcus aureus and 8 μg/mL and 4 μg/mL against Bacillus subtilis, respectively. Furthermore, when compounds 5 and 11 were combined with two commercial antibiotics kanamycin and chloramphenicol, they showed strong synergistic activity at sub‐MIC levels against S. aureus USA300 and B. subtilis 168. Moreover, chloramphenicol turned from a bacteriostatic to a bactericidal agent when combined with compound 11 against B. subtilis 168.