Ultrasound-assisted, low-solvent and acid/base-free synthesis of 5-substituted 1,3,4-oxadiazole-2-thiols as potent antimicrobial and antioxidant agents.

One of the goals of green chemistry is to use environmentally friendly solvents or remove and reduce the volume of harmful spent solvents. In this study, a novel process for the synthesis of 5-substituted 1,3,4-oxadiazole-2-thiol derivatives was proposed via ultrasound-assisted reaction of aryl hydrazides with CS2 (1:1 molar ratio) in some drops of DMF in the absence of basic or acidic catalysts. They were produced in good to excellent yields under easy workup and purification conditions. In order to prove the usefulness of the prepared compounds, their antioxidant, antibacterial, and antifungal potentials were screened by DPPH free radical scavenging, serial twofold microdilution and streak plate methods. Acceptable to significant inhibitory activities were observed with synthesized heterocycles. The results showed that 5-(4-fluorophenyl)-1,3,4-oxadiazole-2-thiol (3c) is an broad-spectrum antimicrobial agent. Many of them displayed remarkable antioxidant properties comparable to standard controls (ascorbic acid and α-tocopherol). Synthesized 1,3,4-oxadiazoles are also potent candidates to treat cancer, Parkinson, inflammatory, and diabetes diseases. Eighteen 5-substituted 1,3,4-oxadiazole-2-thiol derivatives as potent antimicrobial and antioxidant agents were prepared via a new, efficient and green procedure.

Expedient multicomponent synthesis of a small library of some novel highly substituted pyrido[2,3-d]pyrimidine derivatives mediated and promoted by deep eutectic solvent and in vitro and quantum mechanical study of their antibacterial and antifungal activities.

A facile and efficient catalyst- and oxidant-free multicomponent synthesis of a small library of highly substituted pyrido[2,3-d]pyrimidine derivatives is reported. The products were obtained within relatively short reaction times in good to excellent yields in the presence of deep eutectic solvents as media and promoters. Simple purification and reusability of the deep eutectic solvent were the other beneficial factors of the reported protocol. All of the synthesized derivatives were thoroughly screened for possible in vitro antibacterial and antifungal effects against twenty-two bacterial and three fungal pathogens. Some of the prepared pyrido[2,3-d]pyrimidine derivatives showed remarkable antibacterial and antifungal activities in comparison with some typical known antibacterial and antifungal agents. Finally, the derivatives possessing bioactivity effects were subjected to quantum chemical computational studies in order to reveal the probable structural and electronic effects governing the spotted bioactivities. It was found that the observed bioactivities could be best devoted to the HOMO-LUMO energy gap and para delocalization index of the corresponding derivatives.

Green multicomponent synthesis, antimicrobial and antioxidant evaluation of novel 5-amino-isoxazole-4-carbonitriles.

BACKGROUND: Design and synthesis of new inhibitor agents to deal with pathogenic microorganisms is expanding. In this project, an efficient, environmentally friendly, economical, rapid and mild procedure was developed for the synthesis of novel functionalized isoxazole derivatives as antimicrobial potentials. METHODS: Multicomponent reaction between malononitrile (1), hydroxylamine hydrochloride (2) and different aryl or heteroaryl aldehydes 3a-i afforded novel 5-amino-isoxazole-4-carbonitriles 4a-i in good product yields and short reaction times. Deep eutectic solvent K2CO3/glycerol was used as catalytic reaction media. Structure of all molecules were characterized by different analytical tools. In vitro inhibitory activity of all derivatives was evaluated against a variety of pathogenic bacteria including both Gram-negative and Gram-positive strains as well as some fungi. In addition, their free radical scavenging activities were assessed against DPPH. RESULTS: Broad-spectrum antimicrobial activities were observed with isoxazoles 4a, b, d. In addition, antioxidant activity of isoxazole 4i was proven on DPPH. CONCLUSIONS: In this project, compounds 4a, b, d could efficiently inhibit the growth of various bacterial and fungal pathogens. Antioxidant properties of derivative 4i were also significant. These biologically active compounds are suitable candidates to synthesize new prodrugs and drugs due to the presence of different functional groups on their rings.

Multicomponent Solvent-Free Synthesis, Antibacterial Evaluation and QSAR Study of 2-(Bis(benzylthio)methylene) malononitriles.

Multicomponent reaction of malononitrile, carbon disulphide and various benzyl halides was developed as an efficient strategy for the synthesis of 2-(bis(benzylthio)methylene)malononitrile derivatives via two different procedures: (a) in the presence of K2CO3 as a base in acetonitrile and (b) under solvent-free conditions in the presence of triethylamine. Higher yields with shorter reaction times were obtained from the latter procedure. Inhibitory activity of all derivatives was evaluated against 22 pathogenic bacteria including both Gram-negative and Gram-positive strains. Thioether 4b showed broad-spectrum antibacterial activities according to the antibiogram tests. DFT calculations (B3LYP/6-311++G**) were performed to determine the type of drug-receptor interactions. It was found that reversible dipole-dipole forces play a key role in most interactions.

MgO Nanoparticle-Catalyzed Synthesis and Broad-Spectrum Antibacterial Activity of Imidazolidine- and Tetrahydropyrimidine-2-Thione Derivatives.

The biological properties of imidazolidine- and tetrahydropyrimidine-2-thione derivatives such as antiviral, antitumor, anti-inflammatory, and analgesic activities increase the demand for mild and efficient synthetic routes. In this regard, methods such as reaction of diaminoalkanes with carbon disulfide have been developed. However, this method usually suffers from relatively long reaction times, using excess reagents, vigorous reaction conditions, and emission of pernicious hydrogen sulfide gas. In this project, MgO nanoparticle was used as an efficient, non-toxic, recyclable, and economic catalyst to synthesize cyclic five- or six-membered thioureas 3a-h via reaction of 1:1 molar ratios of 1,2- or 1,3-diaminoalkanes 1a-h and carbon disulfide in ethanol at ambient temperature. More interestingly, no hydrogen sulfide emission was detected during the reaction progress. The in vitro antimicrobial properties of synthesized compounds were investigated against 14 different Gram-positive and Gram-negative pathogenic bacteria according to CLSI (Clinical and Laboratory Standards Institute) broth microdilution and disk diffusion methods. The results were compared to those of penicillin, gentamicin, and ceftriaxone, and reported as inhibition zone diameter (IZD), the minimum inhibitory concentration (MIC), and the minimum bactericidal concentration (MBC) values. The best inhibitory effects were observed with imidazolidine-2-thiones 3c and 3d. They were effective against 14 and 11 pathogens, respectively. The structure-activity relationships of the prepared heterocyclic compounds were also studied.

Green One-pot Synthesis of Novel Polysubstituted Pyrazole Derivatives as Potential Antimicrobial Agents.

Various biological properties of natural and synthetic pyrazole derivatives such as anti-inflammatory, antimicrobial, neuroprotective, anticonvulsant, antidepressant and anticancer activities encouraged us to propose a new, fast, green and eco-friendly procedure for the preparation of some novel 5-amino-3-(aryl substituted)-1-(2,4-dinitrophenyl)-1H-pyrazole-4-carbonitriles. They were efficiently synthesized via one-pot two-step process reaction of malononitrile, 2,4-dinitrophenylhydrazine and different benzaldehydes in deep eutectic solvent (DES) glycerol/potassium carbonate. The products yield and reaction times were considerably improved in the presence of applied DES. Antibacterial effects of all newly synthesized pyrazoles in comparison with several common antibiotics were evaluated against a variety of Gram-positive and Gram-negative pathogenic bacteria. In addition to, their inhibitory activities on three fungi were compared to some current antifungal agents. The moderate to good antimicrobial potentials particularly against fungi were observed in the major heterocyclic compounds according to the IZD, MIC, MBC and MFC results.

Cytomegalovirus localization in atherosclerotic plaques is associated with acute coronary syndromes: report of 105 patients.

It has been shown that cytomegalovirus (CMV) is present in coronary atherosclerotic plaques, but the clinical relevance of this presence remains to be elucidated. In this study we sought to examine CMV infection in atherosclerosis patients defined by different methods and to identify the clinical significance of CMV replication in the atherosclerotic plaques. The study included 105 consecutive patients who were admitted to our department and underwent coronary artery bypass grafting (CABG) surgical interventions. Coronary atherosclerotic specimens as well as 53 specimens from the mamillary artery of these same patients were analyzed. Enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods were used for evaluations. The CMV PCR test result was positive for 28 (26.7%) of patients with coronary artery atherosclerosis. After adjusting for other risk factors, coronary artery disease patients with a history of acute coronary syndrome were more likely to be positive for CMV PCR test (P=0.027; odds ratio: 4.2; 95% CI: 1.18-15.0). They were also more likely to have a positive family history for cardiovascular diseases (CVD). This study confirms previous evidence about the replication of CMV virus in the atherosclerotic plaques of coronary arteries and brings clinical significance to this observation by showing a higher prevalence of acute coronary syndromes in those patients with CMV-infected plaques. Our study also suggests a familial vulnerability to CMV replication in the coronary artery walls.

Impact of cardiac rehabilitation on metabolic syndrome in Iranian patients with coronary heart disease: the role of obesity.

BACKGROUND: Due to high prevalence of metabolic syndrome (MetS) and coronary heart disease (CHD) in Iran, and their mutual relationship, we evaluated how comprehensive cardiac rehabilitation (CR) can affect MetS in patients with CHD. METHOD: In this study (1998-2003), we evaluated 547 patients with CHD undergoing comprehensive CR. RESULTS: Cases with MetS decreased from 42.8% to 33.3% after CR program (p < .001). Decrease in high fasting plasma glucose, triglyceridemia, systolic and diastolic blood pressures, and increase in HDL cholesterol, functional capacity, and left ventricular ejection fraction was more prominent in the "MetS but not obese" group. However, total cholesterol, low-density lipoprotein, weight, body mass index, and waist circumference showed a greater decrease in groups with obesity. CONCLUSION: Cardiac rehabilitation is an effective treatment of MetS, particularly in the absence of obesity. This represents an additional argument for the prevention of obesity and the linked insulin resistance.