Novel quinazolinone derivatives: synthesis and antimicrobial activity

4-(4-Oxo-4H-3,1-benzoxazin-2-yl)phenyl-4-methylbenzenesulfonate (2) was prepared and reacted with some primary aromatic amines, e.g., aniline, p-chloro aniline, p-methoxy aniline, p-amino benzoic acid and p-amino acetophenone. It reacted also with some heterocyclic amines, e.g., 2-aminothiazole, 2-aminobenzothiazole, 5-amino-4-phenylazo-2,4-dihydropyrazol-3-one and 3-amino-2-methylquinazolinone and with diamines; e.g., o-phenylenediamine, p-phenylenediamine, ethylenediamine, semicarbazide hydrochloride and thiosemicarbazide under different conditions. On the other hand, compound (2) reacted with both sodium azide and active methylene compounds, e.g., ethylcyanoacetate and ethylacetoacetate to give (19) and (20), respectively. All new prepared compounds were subjected to antimicrobial activity evaluation.     

Disinfection using ultraviolet radiation as an antimicrobial agent: a review and synthesis of mechanisms and concerns

Control of microbes in sensitive health care settings cannot be maintained without effective disinfection methods. Recently, increasing microbial resistance to common chemical agents, including antibiotics, has required the implementation of new approaches to disinfection where such sanitary practices are critical. Pharmaceutical manufacturers and many interrelated industries also have a need for effective disinfection and sanitation strategies. As a result, standard practices that direct and maintain effective microbial controls are established. These practices exploit a thorough understanding of biological processes and manipulate them to preserve the quality and safety of a valuable product. Most biological processes are delicately balanced with their surroundings, or environment. When changes are made to the environment during disinfection, damaged microbes may respond by repairing the immediate damage or by adapting their biological processes through developing a resistance. Unless sound disinfection procedures are consistently applied, new strains of environmental microbes that can utilize multiple resistance markers may be artificially selected. Examples of related drug resistance are currently being studied and managed in many large hospitals, but non-chemical methods are also subject to similar concerns. Here, we review the use of ultraviolet-based disinfection practices, the biological basis for them, and some potential desensitization issues that may develop. Finally, we suggest some approaches to study and practically address these effects.     

Novel thiocyanato complexes with potent cytotoxic and antimicrobial properties

The aim of the present study was to assess the cytotoxic and antimicrobial properties of seven new thiocyanato complexes: Ni(C(9)H(11)N(2)O)(SCN), Cu(C(9)H(11)N(2)O)(SCN), Pd(C(9)H(11)N(2)O)(SCN), Pt(C(9)H(11)N(2) O) (SCN), K[Ti(C(9)H(11)N(2)O)(SCN)(3)], Au(C(9)H(11)N(2)O)(SCN), and K[V(O)(C(9)H(11)N(2)O)(SCN)] (T(1)-T(7), respectively). All the complexes showed toxicity against brine shrimp nauplii (Artemia salina L.). The titanium-based complex, T(5), exhibited potent toxicity, with a lethal concentration 50% (the concentration of test compound that kills 50% of A. salina) value of 1.59 microg mL(-1). These new complexes also exhibited promising antibacterial and antifungal properties. A macrodilution technique was used to estimate the minimum inhibitory concentrations of the seven bioactive complexes. Minimum inhibitory concentrations were found to be 8-64 microg mL(-1) against the tested bacterial species.     

Novel inhibitors of nucleoside triphosphate diphosphohydrolases: chemical synthesis and biochemical and pharmacological characterizations

To elucidate the physiological role played by nucleoside triphosphate diphosphohydrolase (NTPDase; EC 3.6.1.5), adenine nucleotide analogues, modified on the purine ring, have been synthesized and tested as potential inhibitors. Resistance of ATP analogues to hydrolysis and their potency as NTPDase inhibitors were evaluated. For this purpose, a particulate fraction isolated from bovine spleen was used as the enzyme source. Among the synthesized analogues, 8-thiobutyladenosine 5'-triphosphate (8-BuS-ATP) was found to be the most effective nonhydrolyzable competitive inhibitor, with an estimated K(i) of 10 microM. This nonhydrolyzable analogue did not exert any P2X-receptor-mediated effect on endothelium-denuded blood vessels, from the guinea pig mesenteric bed. In agreement with this observation, infusion of the analogue did not cause any significant blood pressure variations of the precontracted vessel. Because in previous studies on isolated turkey erythrocytes and rat astrocytes 8-BuS-ATP was not able to trigger any P2Y(1)-receptor-mediated effect, it therefore appears that this NTPDase inhibitor does not interfere with purinergic receptors.     

Synthesis and antimicrobial activity of hydroxyalkyl- and hydroxyacyl-phenols and their benzyl ethers

New phenolic compounds with hydrophilic side chains were prepared from 4-benzyloxybenzaldehyde and alkenyl magnesium bromides, followed by Sharpless dihydroxylation and hydrogenolytic removal of the benzyl group. The resulting compounds were tested in an agar diffusion assay against gram positive bacteria, gram negative bacteria, and against the fungi Candida glabrata and Aspergillus niger.     

Novel indolyl-pyrimidine derivatives: synthesis,antimicrobial, and antioxidant evaluations

In the present study, a novel series of indolyl-pyrimidines (1–13) were synthesized starting from 4-hydrazinopyrimidine-5-carbonitrile 3. Elemental analysis, IR, ¹H-NMR, ¹³C-NMR, and mass spectral data elucidated structure of newly synthesized compounds. All compounds were screened for their in vitro antibacterial, antifungal, and some for antioxidant activities. Compounds 5, 9g, 9i, and 9j showed pronounced antimicrobial activity against Staphylococcus aureus, Bacillus cereus, Escherichia coli, Candida albicans, and Aspergillus flavus compared to the reference drugs, while compounds 3 and 9g displayed promising free radical scavenging activity and found to be more potent than standard, ascorbic acid (vitamin C). Further, some compounds were evaluated for cytotoxic activity by SRB assay method against human colon carcinoma (CaCo-2) and showed that compounds 4 and 9g were found to be the highly active compared to the reference drug doxorubicin. Their structure and activity relationship were discussed.     

Silver and its application as an antimicrobial agent

This review summarises patents published from 2001 to 2004 on the microcidal properties of silver-releasing materials for healthcare and medicine. The anti-inflammatory, re-epitheliasation and antihaemorrhagic properties of the silver-releasing materials are also disclosed. A biological evaluation of the anti-viral properties of silver tetra-silver tetra-oxide is discussed, but no biological data have been reported to support the claim that silver (I) has anti--viral prop-erties, as disclosed by most of the patents.     

New N-arylamino biquinoline derivatives: microwave-assisted synthesis and their antimicrobial activities

A new series of N-arylamino biquinoline derivatives 5a–x were synthesized under microwave irradiation technique in good yields compared with conventional method and screened for their antimicrobial activity. All the synthesized compounds have been established by elemental analysis, IR, ¹H NMR, ¹³C NMR and mass spectral data. In vitro antimicrobial activity was carried out against three Gram-positive bacteria (Bacillus subtilis, Clostridium tetani, Streptococcus pneumoniae), three Gram-negative bacteria (Escherichia coli, Salmonella typhi, Vibrio cholerae) and two fungal species (Aspergillus fumigatus, Candida albicans) using broth microdilution method. Of the compounds studied, compound 5u exhibited promising antimicrobial activity against Streptococcus pneumoniae and Salmonella typhi.     

New thiazolidine-2,4-diones as antimicrobial and cytotoxic agent

New (Z)-5-substituted-2,4-thiazolidinediones (3a–m) were easily prepared by the condensation of thiazolidine-2,4-dione (1) with suitable aldehydes (2a–m) via microwave irradiation technique. The reaction between (Z)-5-substituted-2,4-thiazolidinediones and 4-(bromomethyl) benzoic acid, using potassium carbonate as base in refluxing acetone, followed by a workup in acidic medium provided 4-(((Z)-5-substituted-2,4-dioxothiazolidin-3-yl)methyl) benzoic acid derivatives (4a–m). The structures of the newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR spectral studies, and elemental analysis. All compounds were evaluated for their in vitro antimicrobial and cytotoxic activities. Antibacterial and antifungal results revealed that most of the compounds showed significant activity where as compounds 4c and 4g are found to be broad spectrum antibacterial and antifungal properties, the MIC values were observed in the range of 2–4 and 2–8?μg/ml, respectively. In MTT cytotoxicity studies, the compound 4g was found most potent. In HeLa, HT29, A549, and MCF-7 cells, the IC₅₀ values were observed in the range of 30–36?μM.     

Rapid synthesis, characterization, anticancer and antimicrobial activity studies of substituted thiadiazoles and their dinucleating ligand metal complexes

Synthesis of 2,5-disubstituted thiadiazoles was accomplished via a conventional method as well as microwave irradiation method. These substituted thiadiazoles were diazotized and coupled with 2,4-pentanedione (AcAc), ethylcyanoacetate (ECA) and malanodinitrile (MN) to get dinucleating ligands. The ligands were isolated, characterized and condensed with Ni (II), Cu (II) and Ru(III) chlorides. These compounds were screened on HL-60 Human leukemia cell Line and U-937 Lymphoma cell lines for anticancer activities. The antimicrobial activity of the ligands and their complexes against bacteria and fungi was also investigated. The effect of metal on the ligand activity is discussed.     

Formation of water-soluble pincer silver(I)-carbene complexes: a novel antimicrobial agent

Silver(I)-2,6-bis(ethanolimidazolemethyl)pyridine hydroxide (4a) and silver(I)-2,6-bis(propanolimidazolemethyl)pyridine hydroxide (4b) are water-soluble silver(I)-carbene complexes that were synthesized in high yield by reacting silver(I) oxide with N-substituted pincer ligands 3 (a = 2,6-bis(ethanolimidazoliummethyl)pyridine diiodide, b = 2,6-bis(propanolimidazoliummethylpyridine)pyridine dibromide). The X-ray crystal structure of 4a is a one-dimensional linear polymer, whereas the mass spectroscopy confirms a monomer in the gas phase. A change in the anion of 4a from a hydroxide to a hexafluorophosphate formed a silver(I)-carbene complex 4c that is dimeric in structure and insoluble in water. The bactericidal activities of the water-soluble silver(I)-carbene complexes were found to be improved over that of silver nitrate.     

Azaanalogues of ebselen as antimicrobial and antiviral agents: synthesis and properties

The different analogues of ebselen-unsubstituted benzisoselenazol-3(2H)-one (2a) 2-pyridylbenzisoselenazol-3(2H)-ones (2b-h) and 7-azabenzisoselenazol-3(2H)-ones (3a-j) were designed as new selenium-containing antiviral and antimicrobial agents and synthesized. Some of them were found in the antiviral assay in vitro to be strong inhibitors of cythopatic activity of herpes simplex virus type 1--HSV-1 (compounds 2a,b,f,h, 3a-j) and encephalomyocarditis virus--EMCV (compounds 2a,h, 3a-f,k,l). The compounds 2a,h and 3a-e,j were found to have an appreciable activity against Gram-positive bacteria (Staphylococcus aureus and Bacillus) in vitro, some of them inhibited growth of pathogenic yeasts (Candida albicans) (3a,b) and filamentous fungi (3a-e,f).     

Comparative study of conventional and microwave-assisted synthesis of some Schiff bases and their potential as antimicrobial agents

A series of Schiff bases (compounds 1–10) were synthesized by condensing heterocyclic/aromatic aldehydes with heterocyclic/aromatic amines through both, conventional method and microwave-assisted synthesis. The compounds were confirmed by means of IR spectroscopy, Mass spectrometry, ¹H NMR and elemental analyses. The compounds were assayed for antibacterial activity against selected strains of Gram positive, Gram negative bacteria and some fungi by zone inhibition method. Minimum inhibitory concentration (MIC) was also determined for each compound. Reaction times were drastically reduced by microwave-assisted synthesis. MIC was as low as 50 μg/ml exhibited by compounds 2 (against Escherichia coli, Aspergillus niger and Penicillium chrysogenum) and 10 (against Bacillus subtilis). The study presents a series of potential antimicrobial agents through efficient and simple reactions and mild reaction conditions, thereby offering a green chemistry approach.     

Synthesis and biological evaluation of novel hydroquinone dimethyl ethers as potential anticancer and antimicrobial agents

The synthesis of two novel series of quinol dimethyl ethers linked to either various functionalities or to some biologically active nitrogenous heterocycles is described. Nine of the newly synthesized quinol dimethyl ethers 5a, b, 9b, 10a, d, 12a, b, and 13a, b were selected by the NCI and were tested initially at a single high dose (10 μM) in the full NCI 60 cell panel. Four of the screened quinol dimethyl ethers bearing unsubstituted phenylhydrazone 5a, 4-chlorophenylhydrazone 5b, 4-chlorophenyl-3-sulfanyl-1,2,4-triazole 9b, as well as 4-chloroanilino-1,3,4-oxadiazole 12b moieties satisfied the threshold antitumor screen. 4-Chlorophenylhydrazone 5b showed very promising results and accordingly was chosen for in vivo antitumor screening. Thus, compound 5b of the series could be considered as the potential lead for development of novel anticancer agents. In addition, compounds 5a–c, 6a–c, 9a–c, 10a, b, d, e, g, h, 11a–c, 12a–c, and 13a–c were screened for their in vitro antimicrobial activity. Some of the tested compounds exhibited special high activity comparable to the reference ampicillin against Pseudomonas aeruginosa and Escherichia coli.     

Synthesis and antimicrobial and antifungal activities of cyclopentene β, β'-triketones and their methyl enol ethers

The natural cyclopentene β, β'-triketone coruscanone B and its methyl enol ether coruscanone A, metabolites of the higher plant Piper coruscans, in addition to 19 of their simple analogs have been synthesized. The antimicrobial activity of the synthesized compounds against Gram-positive (Staphylococcus aureus ATCC 21027) and Gram-negative (Escherichia coli ATCC 15034) bacteria, yeast (Sofale S-04 and Candida albicans KMM455), and fungi (Aspergillus niger KMM4634 and Fusarium oxysporum KMM4639) was studied. The nature and number of substituents at the 4- and 5-positions of the five-membered ring and also the nature of the substituent in the 2-position were found to have a profound effect on the level of activity and the spectrum of antimicrobial action of the tested compounds. Free β, β'ect. It is established that the level of activity and the spectrum of the antimicrobial action of coruscanone A and 2-(1-methoxyethylidene)-4,5-dichlorocyclopent-4-ene-1,3-dione are almost identical to those of the reference drug nitrofungin.     

Microwave-assisted synthesis of novel 1,2,3-triazole derivatives and their antimicrobial activity

An environmentally benign and economic synthesis of 1-[7-(1-benzyl-1H-[1,2,3]triazol-4-ylmethoxy)-2,2-dimethyl-chroman-6-yl]-3-aryl-2-propen-1-ones and 1-[5-(1-benzyl-1H-[1,2,3]triazol-4-ylmethoxy)-2,2-dimethyl-chroman-6-yl]-3-aryl-propen-1-ones is described. The procedure takes place by the 1,3-dipolar cycloaddition (‘‘click-reaction’’) between azides and alkynes catalysed by copper (I) salts. The simplicity of this reaction and the ease of formation and purification of the resulting products have opened new opportunities in generating vast arrays of compounds with biological potential. The structures of the synthesized compounds have been established on the basis of physical and spectral data. All the synthesized compounds were tested in vitro for their antibacterial and antifungal activities. Compounds 8a (R₁=H, R₂=H, R₃=H), 8b (R₁=H, R₂=CH₃, R₃=H), 8d (R₁=OCH₃, R₂=OCH₃, R₃=H), 8e (R₁=OCH₃, R₂=OCH₃, R₃=OCH₃), 13a (R₁=H, R₂=H, R₃=H), 13d (R₁=OCH₃, R₂=OCH₃, R₃=H) and 13e (R₁=OCH₃, R₂=OCH₃, R₃=OCH₃) showed significant antimicrobial properties.