ABSTRACT
Methoxy polyethylene glycol conjugated with coenzyme Q10 (mPEG)-CoQ10 and analog adducts with amino acids as spacers were synthesized as a new drug delivery systems for CoQ10. Alanine and branched chain amino acids (valine, leucine and isoleucine) were conjugated to mPEG by an amide linkage and to CoQ10 by an ester bond. Recently, branched chain amino acids (BCAAs), which are released along with CoQ10, have received increasing attention as 'anti-fatigue' elements. FT-IR and 1H NMR spectroscopic analysis were useful to characterize the synthesized conjugates. Studies in vitro, in buffer solutions at different pH and in the presence of esterase were conducted. The hydrolysis studies showed a specific cleavage dependent on the pH of the medium and by the presence of proteolytic enzymes. The results showed the improvement of the pharmacokinetic properties of CoQ10. The antioxidant activity of the synthesized conjugates was also evaluated by DPPH assay.
Subject(s)
Antioxidants/administration & dosage , Drug Delivery Systems , Polyethylene Glycols/chemistry , Ubiquinone/analogs & derivatives , Amino Acids/chemistry , Antioxidants/chemistry , Antioxidants/pharmacokinetics , Drug Liberation , Esterases/metabolism , Hydrogen-Ion Concentration , Hydrolysis , Proton Magnetic Resonance Spectroscopy , Spectroscopy, Fourier Transform Infrared , Ubiquinone/administration & dosage , Ubiquinone/chemistry , Ubiquinone/pharmacokineticsABSTRACT
Infections caused by non-tuberculous mycobacteria and multidrug-resistant Mycobacterium tuberculosis are difficult to treat, and so new compounds potentially active against these bacteria are being sought. A series of 2-pyridinecarboxamidrazone derivatives, recently synthesized, have been evaluated for their inhibitory activity against 17 Mycobacterium avium isolates; the agar dilution method showed different degrees of susceptibility to the new molecules. Four molecules, three of which are chlorine derivatives, inhibited 94% of the strains tested with an MIC of 32 mg/L. These data indicate that these new pyridine-2-carboxamidrazones merit further study as antimycobacterial agents.
Subject(s)
Antibiotics, Antitubercular/pharmacology , Mycobacterium avium/drug effects , Pyridines/pharmacology , Antibiotics, Antitubercular/chemistry , Humans , Microbial Sensitivity Tests , Mycobacterium avium/isolation & purification , Pyridines/chemistryABSTRACT
[5-(Pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid arylidene-hydrazide derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed a feable activity against a strain of Mycobacterium tuberculosis and a strain of Mycobacterium avium.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Thiadiazoles/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Mycobacterium/drug effects , Structure-Activity Relationship , Thiadiazoles/chemistry , Thiadiazoles/pharmacologyABSTRACT
5-Aryl-1-isonicotinoyl-3-(pyridin-2-yl)-4,5-dihydro-1H-pyrazole derivatives were synthesized and tested for their in vitro antimycobacterial activity. The compounds showed an interesting activity against a strain of Mycobacterium tuberculosis and a human strain of M. tuberculosis H4.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Antitubercular Agents/chemical synthesis , Pyrazoles/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Pyrazoles/chemistry , Pyrazoles/pharmacology , Structure-Activity RelationshipABSTRACT
6-[(Arylmethylenamino)carbonyl]-3-(pyridin-2-yl)-4H-1,2,4-triazin-5-one derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed interesting activity against a strain of Mycobacterium tuberculosis.
Subject(s)
Antitubercular Agents/pharmacology , Triazines/pharmacology , Antitubercular Agents/chemical synthesis , Antitubercular Agents/chemistry , Molecular Structure , Mycobacterium avium/drug effects , Mycobacterium tuberculosis/drug effects , Triazines/chemical synthesis , Triazines/chemistryABSTRACT
N1-[1-[3-aryl-1-(pyridin-2,3-, and 4-yl)-3-oxo[propyl]-2- pyridinecarboxamidrazone derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed interesting activity against a strain of Mycobacterium tuberculosis and a strain of Mycobacterium avium.
Subject(s)
Anti-Bacterial Agents/pharmacology , Mycobacterium avium/drug effects , Mycobacterium tuberculosis/drug effects , Pyridines/chemical synthesis , Pyridines/pharmacology , Microbial Sensitivity Tests , Pyridines/chemistry , Spectrum AnalysisABSTRACT
A series of pyridine-2-carboxamidrazone and quinoline-2-carboxamidrazone derivatives containing the indole moiety was prepared. Some of the synthesized compounds showed an interesting in vitro antimycobacterial activity against a strain of Mycobacterium tuberculosis.
Subject(s)
Antitubercular Agents/chemical synthesis , Mycobacterium tuberculosis/drug effects , Antitubercular Agents/pharmacology , Microbial Sensitivity TestsABSTRACT
A series of 5-substituted 2-arylamino-1,3,4-thiadiazole derivatives was prepared. The antimicrobial activity of these compounds against some strains of bacteria and a strain of Candida albicans was determined, together with that of the corresponding thiosemicarbazone derivatives, which are intermediates in the synthetical procedure.
Subject(s)
Anti-Infective Agents/chemical synthesis , Bacteria/drug effects , Thiadiazoles/chemical synthesis , Anti-Bacterial Agents , Anti-Infective Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Candida albicans/drug effects , Escherichia coli/drug effects , Gram-Positive Bacteria/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Thiadiazoles/pharmacologyABSTRACT
After preliminary in vitro screening of 15 newly synthesized compounds belonging to the chemical class of N1-(aryliden)-4-pyridinecarboxyamidrazones against Mycobacterium tuberculosis reference strain H37 Rv, we determined the minimum inhibitory concentrations (MICs) of the six most promising chemicals against different species of Mycobacterium and different strains of M. tuberculosis. The agar dilution method was employed against M. gordonae, M. bovis, M. kansasi, M. avium, M. fortuitum and on eighteen different strains of M. tuberculosis, isolated from human bronchial aspirates. The results obtained confirmed that the newly synthesized chemicals possessed a very interesting antitubercular activity, their MICs ranging from 4 micrograms/ml to 16 micrograms/ml.
Subject(s)
Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Pyridines/pharmacology , Antitubercular Agents/chemistry , Antitubercular Agents/classification , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/chemistry , Mycobacterium tuberculosis/classification , Pyridines/chemistry , Species SpecificityABSTRACT
A series of N1-aryliden-4-pyridinecarboxyamidrazone derivatives was prepared. Some of the synthesized compounds showed interesting in vitro antimycobacterial activity against some strains of Mycobacterium and clinical isolates of Mycobacterium tuberculosis.
Subject(s)
Mycobacterium/drug effects , Pyridines/chemical synthesis , Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Drug Resistance, Microbial , Humans , Microbial Sensitivity Tests , Mycobacterium avium/drug effects , Mycobacterium tuberculosis/drug effects , Pyridines/pharmacologyABSTRACT
A series of N1-aryliden-2-pyridincarboxyamidrazone derivatives was prepared. Some of the synthesized compounds showed interesting in vitro antimycobacterial activity against some strains of Mycobacterium and clinical isolates of Mycobacterium tuberculosis.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Mycobacterium/drug effects , Pyridines/chemical synthesis , Anti-Bacterial Agents/pharmacology , Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Drug Resistance, Microbial , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Pyridines/pharmacology , Structure-Activity RelationshipABSTRACT
A rapid, sensitive and specific reversed phase HPLC method for the simultaneous assay of amiodarone and its major metabolite desethylamiodarone in human serum has been developed. This method is suitable for pharmacokinetic studies and for monitoring of the drug and metabolite concentrations in serum of patients on both short and long-term therapy with amiodarone.
Subject(s)
Amiodarone/analogs & derivatives , Amiodarone/blood , Chromatography, High Pressure Liquid , HumansABSTRACT
After preliminary in vitro screening of 17 newly synthesized compounds belonging to the chemical class of N1-(aryliden)-2-pyridinecarboxyamidrazones, active against Mycobacterium tuberculosis H37Rv, the minimum inhibitory concentrations (MICs) of the ten most promising agents against three clinical isolates were determined by agar dilution. Compounds 12 and 14 were the most active, each inhibiting strain H37Rv at concentrations of 8 microg/ml and having a MIC of 16 microg/ml against the human isolates. The results obtained in this preliminary study confirmed the interesting antitubercular properties of these newly synthesized compounds and allowed us to carry out our investigations over a large number of isolated clinical strains.
Subject(s)
Mycobacterium tuberculosis/drug effects , Pyridines/pharmacology , Humans , Microbial Sensitivity TestsABSTRACT
The synthesis and in vitro antifungal activity of some pyridincarboxyamidrazone derivatives are described. 2-pyridincarboxyamidrazone derivative (IIa) in comparison with miconazole showed an interesting even if low antimycotic activity.
Subject(s)
Amidines/pharmacology , Antifungal Agents/chemical synthesis , Pyridines/pharmacology , Amidines/chemical synthesis , Aspergillus niger/drug effects , Candida albicans/drug effects , Chemical Phenomena , Chemistry , Culture Media , Fungi/drug effects , Furans/chemical synthesis , Furans/pharmacology , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Pyridines/chemical synthesis , Thiophenes/chemical synthesis , Thiophenes/pharmacology , Trichophyton/drug effectsABSTRACT
A series of 2-arylamino-1,3,4-thiadiazole derivatives was synthesized with the aim to find new antihypertensive compounds. The antihypertensive activity of some of these compounds was examined intraperitoneally in conscious spontaneously hypertensive rats (SHR). The tested compounds showed activity, but none of these possessed a higher potency than the reference substance guanabenz.
Subject(s)
Antihypertensive Agents/chemical synthesis , Thiadiazoles/chemical synthesis , Animals , Antihypertensive Agents/administration & dosage , Blood Pressure/drug effects , Chemical Phenomena , Chemistry , Heart Rate/drug effects , Male , Rats , Rats, Inbred SHR , Thiadiazoles/administration & dosage , Thiadiazoles/pharmacology , Time FactorsSubject(s)
Antihypertensive Agents/chemical synthesis , Guanidines/chemical synthesis , Hydrazines/chemical synthesis , Pyridines/chemical synthesis , Triazoles/chemical synthesis , Animals , Blood Pressure/drug effects , Guanidines/pharmacology , Hydrazines/pharmacology , Male , Pyridines/pharmacology , Rats , Rats, Inbred SHR , Triazoles/pharmacologyABSTRACT
The synthesis of new benzylidenaminoguanidine compounds is described. Some of these compounds were tested for antihypertensive activity in conscious unrestrained spontaneously hypertensive rats. The compounds examined possess a significant antihypertensive activity, qualitatively different from that of clonidine. For the tested compounds, the absence of the transient rise in blood pressure, which appears immediately after administration of clonidine-like drugs, is noteworthy.