Synthesis and study of antibacterial and antifungal activities of novel 1-[2-(benzoxazol-2-yl)ethoxy]- 2,6-diarylpiperidin-4-ones

Some novel benzoxazolylethoxypiperidones have been synthesized and their antibacterial activity against streptococcus faecalis, bacillus subtilis, escherichia coli, staphylococcus aureus aand pseudomonas aeruginosa and antifungal activity against Candida-6, Candida albicans, Aspergillus niger, Candida-51 and Aspergillus flavus were evaluated. Compounds 37, 38 and 39 exerted potent in vitro antibacterial activity against Streptococcus faecalis while compounds 40 and 41 exhibited potent in vitro antifungal activity against Candida-51.     

Synthesis and in vitro microbiological evaluation of imidazo(4,5-b)pyridinylethoxypiperidones

A series of imidazo(4,5-b)pyridinylethoxypiperidones was designed, synthesized and characterized for evaluation of potential antibacterial activity against Bacillus subtilis, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa and antifungal activity against Candida albicans-6, Candida albicans, Aspergillus niger, Candida albicans-51 and Aspergillus flavus. Structure-activity relationship led to the conclusion that compound 39 exerted strong in vitro antibacterial activity against Bacillus subtilis and Staphylococcus aureus whereas compounds 38 and 39 displayed promising antifungal activity against Aspergillus flavus. The interesting antimicrobial profile of compound 39 led us to select this derivative for further development.     

Synthesis, characterization and in vitro biological studies of novel cyano derivatives of N-alkyl and N-aryl piperazine

Cyano derivatives of N-alkyl and N-aryl piperazine have been synthesized and screened for antibacterial and antifungal activities. All the synthesized compounds showed the antibacterial activity against pathogenic strains of Staphylococcus aureus (MTCCB 737), Pseudomonas aeruginosa (MTCCB 741), Streptomyces epidermidis (MTCCB 1824) and Escherichia coli (MTCCB 1652) and antifungal activity against pathogenic strains of Aspergillus fumigatus (ITCC 4517), Aspergillus flavus (ITCC 5192) and Aspergillus niger (ITCC 5405). All compounds showed mild to moderate antimicrobial activity. However, compounds 3c, 4a and 6 showed potent antibacterial activity against pathogenic strains used in the study. Compounds 3a, 3b, 4b, and 4d showed mild to moderate antifungal activity against Aspergillus pathogenic strains. The compounds reported in this study were assessed for there cytotoxicity using MTT colorimetric assay on Hela cells. All the compounds showed cell viability more than the control drug gentamicin, with compound 2 having highest i.e. 95% cell viability.     

Synthesis, stereochemistry and antimicrobial evaluation of some N-morpholinoacetyl-2,6-diarylpiperidin-4-ones

In a search for new leads towards potent antimicrobial agents, an array of novel N-morpholinoacetyl-2,6-diarylpiperidin-4-ones has been synthesized and their in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi and antifungal activity against Candida albicans, Rhizopus sp., Aspergillus niger and Aspergillus flavus were evaluated. Structure and stereochemistry of all the N-morpholinoacetyl-2,6-diarylpiperidin-4-ones have been analyzed using (1)H and (13)C NMR spectroscopic techniques. In all the cases, amide N-CO group is preferentially in coplanar orientation with respect to the dynamically averaged plane of the piperidone ring. Further, all the symmetrically substituted compounds 19, 23, 24, 26 and 27 are expected to adopt half boat conformations while other compounds 20-22 and 25 adopt twist-boat conformations. Structure-activity relationship results for these nine compounds have shown that compounds 26 and 27 exerted excellent antibacterial activity against all the bacterial strains used except 27 against S. aureus. Against C. albicans and A. flavus, compound 24 recorded excellent antifungal activities while against Rhizopus sp., compound 25 showed potent activities. The obtained results may be used as key step for the building of novel chemical compounds with interesting antimicrobial profiles comparable to that of the standard drugs.     

Synthesis, stereochemistry and antimicrobial evaluation of t(3)-benzyl-r(2),c(6)-diarylpiperidin-4-one and its derivatives

In a wide research program toward new and efficient antimicrobial agents, a series of t(3)-benzyl-r(2),c(6)-diarylpiperidin-4-ones (1-7) were synthesised and tested for their in vitro antibacterial and antifungal activities. Also, the structures and their stereochemistry of these synthesised compounds 1-7 were characterized by IR, high resolution (1)H NMR, (13)C NMR and (1)H-(13)C COSY spectra. The analysis of coupling constants of compounds 1-5 reveals that they exist in normal chair conformation with equatorial orientations of all the substituents. The spectra of 6 and 7 reveal the presence of two isomers labeled as E (carbonyl carbon is anti to benzyl group at C-3) and Z (carbonyl carbon is syn to benzyl group at C-3) in solution and the coupling constants ruled out the possibility of normal chair conformation. From the theoretical studies and coupling constant values the favoured conformation for the Z- and E-isomers of 6 and 7 was found to be the boat conformations. Their antibacterial activity against Streptococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae and antifungal activity against Cryptococcus neoformans, Candida 6, Candida 51, Aspergillus niger and Aspergillus flavus were also evaluated.     

Synthesis of 6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid derivatives as potential antimicrobial agents

In the present study, a series of 1-ethyl/benzyl-6-fluoro-7-(substituted piperazin-1-yl)1,4-dihydro-4-oxo-quinoline-3-carboxylic acid were synthesized and characterized by IR, 1H-NMR, mass spectral and elemental analysis. The in vitro antibacterial and antifungal activities of the compounds were evaluated by paper disc diffusion method. The minimum inhibitory concentrations (MIC) of the compounds were also determined by agar streak dilution method. The in vivo antibacterial activity of the compounds against Escherichia coli was also evaluated by mouse protection test. All the compounds exhibited significant antibacterial and weak antifungal activities. The in vivo antibacterial activity (ED50) against E. coli was 50-160 mg kg(-1) in the order of 7<9<8<10. 1-ethyl-6-fluoro-7-(2,5-dioxo-piperazin-1-yl)1,4-dihydro-4-oxo-quinoline-3-carboxylic acid (7) was found to exhibit the most potent in vitro antimicrobial activity with MIC of 4.1, 3.1, 3.1, 2.4, 1, 1, 25 and >100 microg mL(-1) against Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus luteus, Bacillus cereus, E. coli, Klebsiella pneumoniae, Candida albicans and Aspergillus niger.     

Synthesis, spectral characterization, in vitro antibacterial, antifungal and cytotoxic activities of Co(II), Ni(II) and Cu(II) complexes with 1,2,4-triazole Schiff bases

A series of metal complexes of cobalt(II), nickel(II) and copper(II) have been synthesized with newly synthesized biologically active 1,2,4-triazole Schiff bases derived from the condensation of 3-substituted-4-amino-5-mercapto-1,2,4-triazole and 8-formyl-7-hydroxy-4-methylcoumarin, which have been characterized by elemental analyses, spectroscopic measurements (IR, UV-vis, fluorescence, ESR), magnetic measurements and thermal studies. Electrochemical study of the complexes is also reported. All the complexes are soluble to limited extent in common organic solvents but soluble to larger extent in DMF and DMSO and are non-electrolytes in DMF and DMSO. All these Schiff bases and their complexes have also been screened for their antibacterial (Escherichia coli, Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa and Salmonella typhi) and antifungal activities (Aspergillus niger, Aspergillus flavus and Cladosporium) by MIC method. The brine shrimp bioassay was also carried out to study their in vitro cytotoxic properties.     

Antimicrobial studies of some novel quinazolinones fused with [1,2,4]-triazole, [1,2,4]-triazine and [1,2,4,5]-tetrazine rings

Three series of novel and new fused heterocyclic systems, viz. triazolo[4,3-a]-quinazolin-7-ones (4), [1,2,4,5]-tetrazino[4,3-a]-quinazolin-8-ones (6) and indolo[2,3-c][1,2,4]-triazino[4,3-a]-quinazolin-8-ones (8) have been synthesized from the key intermediate 3-(substituted-phenyl)-2-hydrazino-quinazolin-4-ones (3). Thus, condensation of (3) with appropriate aromatic acids in the presence of DCC in dichloromethane afforded the fused system (4), while reaction of (3) with isatin in methanol gave the corresponding Schiff base (7) which on cyclodehydration furnished another fused heterocyclic system (8). The intermediate (3) on refluxing with substituted-phenylisothiocyanate gave the substituted-thiosemicarbazide (5), which on oxidative cyclization with bromine in CCl(4) furnished the novel fused system (6). The structures of intermediate and final compounds have been determined by means of IR, (1)H NMR, (13)C NMR, UV and elemental analysis. All the synthesized compounds have been screened for their antibacterial activity against gram-negative bacteria, Escherichia coli, Pseudomonas aeruginosa and gram-positive bacteria, Streptococcus pneumoniae, Bacillus subtilis, as well as demonstrated significant antifungal activity against fungi viz. Candida albicans, Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger.     

Synthesis and antifungal activity of 2/3-arylthio- and 2,3-bis(arylthio)-5-hydroxy-/5-methoxy-1,4-naphthoquinones

2/3-Arylthio- and 2,3-bis(arylthio)-5-hydroxy-/5-methoxy-1,4-naphthoquinones 5-9 were synthesized and tested for in vitro antifungal activity against Candida species and Aspergillus niger. The synthesized compounds 5-9 generally showed good activities against Candida albicans and C. tropicalis. The results suggest that the 1,4-naphthoquinones 5-9 would be potent antifungal agents.     

Phytochemical and antimicrobial study of an antidiabetic plant: Scoparia dulcis L

The antimicrobial and antifungal effects of different concentrations of chloroform/methanol fractions of Scoparia dulcis were investigated. The isolated fractions were tested against different bacteria like Salmonella typhii, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Proteus vulgaris and fungal strains such as Alternaria macrospora, Candida albicans, Aspergillus niger, and Fusarium oxysporum. The isolated fractions exhibited significant antimicrobial and antifungal activity against all the tested organisms compared with respective reference drugs. The isolated fractions of S. dulcis showed properties like antimicrobial and antifungal activities that will enable researchers in turn to look for application-oriented principles.     

Synthesis, structure and biological activity of pseudopeptidic macrolides based on an amino alcohol

A series of new pseudopeptidic macrolides 2a-f based on an amino alcohol were synthesized and evaluated for in vitro antibacterial and antifungal activities. The structure-activity relationships of these compounds were studied and the results showed that compounds 2a and 2d exhibited moderate antibacterial activity against Staphylococcus aureus, Bacillus subtilis and Escherichia coli, whereas compound 2e showed potent antifungal activity against all the fungal species tested, showing a promising broad-spectrum antifungal activity. All the compounds have been studied in vitro for the hemolytic activity as a measure of their cytotoxicity, showing that these compounds have low lytic properties.     

Physicochemical and biological characterization of novel macrocycles derived from o-phthalaldehyde

A series of novel macrocyclic compounds were synthesized by the condensation of o-phthalaldehyde with aromatic amino alcohols followed by treatment with 1,2-dibromoethane or 1,3-dibromopropane in non-template method. The structural features of the isolated macrocycles have been determined from the microanalytical, IR, (1)H, (13)C NMR and mass spectral studies. Antimicrobial activities of these macrocyclic compounds were tested against the gram-positive (Bacillus subtilis, Staphylococcus aureus) and gram-negative (Escherichia coli, Klebsiella pneumoniae) bacteria and found to exhibit potential antibacterial activity. The macrocycles were also tested in vitro to evaluate their activity against fungi, namely, Aspergillus flavus (A. flavus) and Fusarium species.     

Synthesis of Schiff bases of 4-(4-aminophenyl)-morpholine as potential antimicrobial agents

In the present study, a novel series of Schiff bases of 4-(4-aminophenyl)-morpholine were synthesised and characterised by IR, 1H-NMR, 13C-NMR, Mass spectral and elemental analysis. The compounds were screened for antibacterial (Staphylococcus aureus (ATCC 9144), Staphylococcus epidermidis (ATCC 155), Bacillus cereus (ATCC 11778), Micrococcus luteus (ATCC 4678), and Escherichia coli (ATCC 25922)) and antifungal (Candida albicans (ATCC 2091) and Aspergillus niger (ATCC 9029)) activities. The minimum inhibitory concentrations of the compounds were also ascertained by agar streak dilution method. 4-(4-(4-Hydroxy-benzylidene-imino)phenyl)-morpholine (7) was found to be the most potent antimicrobial activity with MIC of 25, 19, 21, 16, 29, 20 and 40 microg/ml against S. aureus, S. epidermidis, B. cereus, M. luteus, E. coli, C. albicans and A. niger, respectively. All the other compounds exhibited moderate activity against the bacterial and fungal organisms tested.     

In vitro antimicrobial activity of the novel polymeric guanidine Akacid plus

The bactericidal and fungicidal activity of Akacid plus, a novel polymeric compound of the cationic family of disinfectants, was compared with chlorhexidine digluconate using quality control strains of Staphylococcus aureus, Enterococcus hirae, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger. In vitro activity was determined using the quantitative suspension tests described by the European Committee for Standardization. These use concentrations of 0.01-0.5% against bacterial strains/C. albicans, with 0.5-4% against A. niger, and exposure times of 5, 15 and 60 min in the presence and absence of 0.3% bovine albumin and with dilution in distilled and hard water. In the basic quantitative suspension test, Akacid plus destroyed all bacterial pathogens at a concentration of 0.1% in < or =5 min. Chlorhexidine was also highly active against S. aureus, E. coli and P. aeruginosa, but failed to eliminate E. hirae within 5 min. A high organic load reduced the bactericidal activity of both disinfectants slightly. Akacid plus showed fungicidal activity against C. albicans within 15-60 min and eliminated A. niger at a concentration of 1% in 5 min of contact. Chlorhexidine was fungicidal against C. albicans, but not against A. niger.     

牛角瓜花的抑菌活性研究

目的以牛角瓜花为实验材料,对其抑菌活性进行研究。方法以索氏提取法得到牛角瓜花的石油醚、氯仿、乙酸乙酯和甲醇的粗提物,并选择白色念珠菌等6种真菌和金黄色葡萄球菌等7种细菌,采用纸片琼脂扩散法对不同溶剂粗提物进行抑菌活性测定。结果牛角瓜花的石油醚粗提物对黄曲霉、枯草芽孢杆菌和尖孢镰刀菌表现出优秀的抑菌效果,抑菌圈直径分别为13.37、12.81、12.25 mm,均优于阳性对照氟康唑和两性霉素B的抑菌活性;氯仿粗提物对枯草芽孢杆菌、大肠埃希菌和白色念珠菌表现出良好的抑菌活性,抑菌圈直径分别为11.73、11.10、10.84 mm;乙酸乙酯和甲醇粗提物的抑菌效果较弱,乙酸乙酯粗提物对黄曲霉的抑菌圈直径为12.81 mm,甲醇粗提物对黑曲霉的抑菌圈直径为9.90 mm,且两种粗提物对其他供试菌有较弱或无抑菌效果。结论牛角瓜花中的化学成分在不同溶剂中的溶解性不同,使得4种溶剂粗提物的抑菌能力存在差异。     

Synthesis, stereochemistry, and antimicrobial evaluation of substituted piperidin-4-one oxime ethers

In a wide search program toward new and efficient antimicrobial agents, a series of substituted piperidin-4-one oxime ethers (5a-5k) was synthesized and tested for their in vitro antibacterial and antifungal activities. Also, the structures of these oxime ethers and their relative stereochemistries have been investigated by nuclear magnetic resonance spectroscopy. In all the oxime ethers synthesized, the orientation of the N-O bond of the oxime ether moiety syn to C-5 (E-isomer) was deduced based on (1)H NMR and (13)C NMR spectra. It was found that the sterically less hindered compounds, either C-3 (H) and C-5 (H)- or C-3 (Me) and C-5 (H) -substituted ones 5a, 5c, 5d, 5f, 5g, 5i and 5j prefer chair conformation, whereas the sterically more hindered C-3 (Me) and C-5 (Me) -substituted ones 5b, 5e, 5h, and 5k prefer twist-boat conformation. Among the oxime ethers tested, 1,3,5-trimethyl-2,6-diphenylpiperidin-4-one O-(2-chlorophenylmethyl)oxime (5h) exhibited good antibacterial property against Bacillus subtilis, with minimum inhibitory concentration (MIC) closer to that of reference drug, streptomycin. Compounds, 1,3-dimethyl-2,6-diphenylpiperidin-4-one O-(2-chlorophenylmethyl)oxime (5g) and 1,3-dimethyl-2,6-diphenylpiperidin-4-one O-(2-bromophenylmethyl)oxime (5j) showed potent antifungal activity against Aspergillus flavus and Candida-51, respectively. The later compound 5j is more active than the reference drug while the activity of the former one 5g is similar to that of the reference drug, amphotericin B in terms of MIC. The present results may be used as key steps for the construction of novel chemical entities with better pharmacological profiles than standard drugs.     

Synthesis, crystal structure and antimicrobial activity of deoxybenzoin derivatives from genistein

A series of deoxybenzoin derivatives from genistein were synthesized and their structures were elucidated by (1)H NMR, mass spectral data and micro analyses. The structures of 2, 7 and 10 were determined by single-crystal X-ray analysis. These obtained compounds were evaluated for their assayed antibacterial (Bacillus subtilis, Escherichia coli, Pseudomonas fluorescence and Staphylococcus aureus) and antifungal (Aspergillus niger, Candida albicans and Trichophyton rubrum) activities by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method. Most compounds have displayed comparable antibacterial activity against bacterial. On the basis of the biological results, structure-activity relationships are discussed.     

Synthesis and antimicrobial activities of Schiff bases derived from 5-chloro-salicylaldehyde

A series of Schiff bases (compounds 1-26) were synthesized by reacting 5-chloro-salicylaldehyde and primary amines, 15 (compounds 2-4, 6, 7, 10, 12-17, 23, 25 and 26) of which were first reported. The chemical structures of these compounds were confirmed by means of (1)H NMR, (13)C NMR, ESI-MS and elemental analyses. The compounds were assayed for antibacterial (Bacillus subtilis, Escherichia coli, Pseudomonas fluorescence and Staphylococcus aureus) and antifungal (Aspergillus niger, Candida albicans and Trichophyton rubrum) activities by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl trtrazolium bromide) method. Among the compounds tested, (E)-4-chloro-2-((4-fluorobenzylimino)methyl)phenol (2) showed the most favorable antimicrobial activity with MICs of 45.2, 1.6, 2.8, 3.4, and 47.5 microg/mL against B. subtilis, E. coli, P. fluorescence, S. aureus and A. niger, respectively.     

8种氟喹诺酮类药物的体外敏感性

目的比较大肠埃希菌、铜绿假单胞菌和金黄色葡萄球菌对8种氟喹诺酮类药物的体外抗菌活性. 方法按NCCLS推荐的标准纸片扩散法(K-B法)对69株大肠埃希菌、84株铜绿假单胞菌和82株金黄色葡萄球菌进行8种三代氟喹诺酮药物的体外敏感性实验. 结果对于大肠埃希菌和铜绿假单胞菌,环丙沙星的体外抗菌活性最强;对于金黄色葡萄球菌,虽环丙沙星的敏感率低于氧氟沙星、左氧氟沙星及司帕沙星等,但并未提示差异有显著性(P>0.05). 结论 8种帕喹诺酮类药物显示明显的交叉耐药性,环丙沙星的体外敏感性结果对于临床应用三代氟喹诺酮类药物具有一定的指导意义.     

Synthesis, biological evaluation and 2D-QSAR analysis of benzoxazoles as antimicrobial agents

A new series of 5(or 6)-nitro/amino-2-(substituted phenyl/benzyl)benzoxazole derivatives were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and their drug-resistant isolate. Microbiological results indicated that the synthesized compounds possessed a broad spectrum of activity against the tested microorganisms at MIC values between > 400 and 12.5 microg/ml. The results against B. subtilis, P. aeruginosa, drug-resistant B. subtilis, drug-resistant E. coli, and C. albicans isolate for these kinds of structures are quite encouraging. The 2D-QSAR analysis of a set of newly and previously synthesized benzoxazoles tested for growth inhibitory activity against B. subtilis ATCC 6633 was performed by using the multivariable regression analysis. The activity contributions for substituent effects of these compounds were determined from the correlation equation for predictions of the lead optimization.