Methylxanthines especially theophylline have been recognized as potent bronchodilators for the relief of acute asthma for over 65 years. Recently, it was found that bacterial infection plays a role in asthma pathogenesis. Accordingly, the present work involves the synthesis of 6-(4-(un)substituted phenyl)thiazolo[2,3-f]theophyllines 2a-g and different series of 8-(1,2,4-triazol-3- ylmethylthio)theophyllines 6-9. The chemical structures of the target compounds were proved by IR, 1H NMR, 13C NMR, EI-MS and HRMS spectroscopic techniques along with elemental analyses. The bronchodilator activity of fifteen compounds was determined in vivo by acetylcholine induced bronchospasm in anaesthetized guinea pigs. Results revealed that all compounds showed moderate to good activity; in addition, five compounds exhibited a bronchodilator activity nearly similar to that of aminophylline as a standard. The antibacterial activity of all the target compounds was investigated in vitro against both Gram-positive and Gram-negative bacterial strains. Results revealed that some compounds showed more potent antibacterial activity than ampicillin as a standard. Acute toxicity study for four target compounds revealed that none of these derivatives showed significant toxicity up to 300 mg/kg. It was found that compound 8c combined both promising bronchodilator and antibacterial activities. This compound could be subjected for further investigations as a new possible candidate in the treatment of bronchial asthma.

Methylxanthines especially theophylline have been recognized as potent bronchodilators for the relief of acute asthma for over 50 years. Recently, it was found that bacterial infection has a role in asthma pathogenesis. Accordingly, the present work involves the synthesis of different series of 8-substituted (aryl, aralkyl,cycloalkyl, and heteroaryl)-1,3-dimethylxanthines. The chemical structures of these compounds were elucidated by IR, 1H NMR, 13C NMR, elemental analyses, and high resolution EI-MS or FAB-MS for some compounds. The bronchodilator activity was evaluated using acetylcholine induced bronchospasm in guinea pigs and most of the compounds showed significant anti-bronchoconstrictive activity in comparison with aminophylline as a standard. Also, the antibacterial activity of all the target compounds was investigated in-vitro against Gram-positive and Gram-negative bacteria using ampicillin as a reference drug. Results showed that some of the tested compounds have potent antibacterial activity. A pharmacophore model was computed to get useful insight on the essential structural features of bronchodilator activity.

Methylxanthines especially theophylline have been recognized as potent bronchodilators for the relief of acute asthma for over 50 years. Recently, it was found that bacterial infection has a role in asthma pathogenesis. Accordingly, the present work involves the synthesis of different series of 8-substituted (aryl, aralkyl,cycloalkyl, and heteroaryl)-1,3-dimethylxanthines. The chemical structures of these compounds were elucidated by IR, 1H NMR, 13C NMR, elemental analyses, and high resolution EI-MS or FAB-MS for some compounds. The bronchodilator activity was evaluated using acetylcholine induced bronchospasm in guinea pigs and most of the compounds showed significant anti-bronchoconstrictive activity in comparison with aminophylline as a standard. Also, the antibacterial activity of all the target compounds was investigated in-vitro against Gram-positive and Gram-negative bacteria using ampicillin as a reference drug. Results showed that some of the tested compounds have potent antibacterial activity. A pharmacophore model was computed to get useful insight on the essential structural features of bronchodilator activity.

Methylxanthines especially theophylline have been recognized as potent bronchodilators for the relief of acute asthma for over 50 years. Recently, it was found that bacterial infection has a role in asthma pathogenesis. Accordingly, the present work involves the synthesis of different series of 8-substituted (aryl, aralkyl,cycloalkyl, and heteroaryl)-1,3-dimethylxanthines. The chemical structures of these compounds were elucidated by IR, 1H NMR, 13C NMR, elemental analyses, and high resolution EI-MS or FAB-MS for some compounds. The bronchodilator activity was evaluated using acetylcholine induced bronchospasm in guinea pigs and most of the compounds showed significant anti-bronchoconstrictive activity in comparison with aminophylline as a standard. Also, the antibacterial activity of all the target compounds was investigated in-vitro against Gram-positive and Gram-negative bacteria using ampicillin as a reference drug. Results showed that some of the tested compounds have potent antibacterial activity. A pharmacophore model was computed to get useful insight on the essential structural features of bronchodilator activity.

Methylxanthines especially theophylline have been recognized as potent bronchodilators for the relief of acute asthma for over 50 years. Recently, it was found that bacterial infection has a role in asthma pathogenesis. Accordingly, the present work involves the synthesis of different series of 8-substituted (aryl, aralkyl,cycloalkyl, and heteroaryl)-1,3-dimethylxanthines. The chemical structures of these compounds were elucidated by IR, 1H NMR, 13C NMR, elemental analyses, and high resolution EI-MS or FAB-MS for some compounds. The bronchodilator activity was evaluated using acetylcholine induced bronchospasm in guinea pigs and most of the compounds showed significant anti-bronchoconstrictive activity in comparison with aminophylline as a standard. Also, the antibacterial activity of all the target compounds was investigated in-vitro against Gram-positive and Gram-negative bacteria using ampicillin as a reference drug. Results showed that some of the tested compounds have potent antibacterial activity. A pharmacophore model was computed to get useful insight on the essential structural features of bronchodilator activity.

The first total synthesis of cystobactamid 507, a member of a class of new natural products with strong inhibitory activity towards bacterial topoisomerases, is reported. Synthetic key challenges are the central tetrasubstitued arene and the low chemical reactivity of anilines and ortho-phenolic and isopropoxy-substituted benzoic acids. Biological evaluations demonstrate that cystobactamid 507 inhibits several Gram-positive pathogens but at significantly lower concentrations than described for the larger members of this natural product family.

The emergence of bacterial resistance requires the development of new antibiotics with an alternative mode of action. Based on class I, developed in our previous study, a new series of RNA polymerase (RNAP) inhibitors targeting the switch region was designed. Feasible synthetic procedures for the aryl-ureido-heterocyclic-carboxylic acids were developed including three regioisomeric thiophene classes (II–IV), as well as three isosteric furan (V, VI) and thiazole (VII) classes. Biological evaluation using a RNAP transcription inhibition assay revealed that class II compounds possess the same activity as the parent class I, whereas classes III, V–VII were active, however with lower potency. Structure–activity relationship (SAR) studies, supported by molecular modeling, elucidated the structural requirements necessary for interaction with the binding site. Beside the RNAP inhibitory effects, the new compounds displayed good antibacterial activities against Gram positive bacteria and the Gram negative E. coli TolC strain. Moreover, they showed no cross resistance with the clinically used RNAP inhibitor rifampicin (Rif) and a lower rate of resistance compared to Rif.

Aim: Antibiotic resistance has become a major health problem. The σ70:core interface of bacterial RNA polymerase is a promising drug target. Recently, the coiled-coil and lid-rudder-system of the β’ subunit has been identified as an inhibition hot spot. Materials & methods & Results: By using surface plasmon resonance-based assays, inhibitors of the protein–protein interaction were identified and competition with σ70 was shown. Effective inhibition was verified in an in vitro transcription and a σ70:core assembly assay. For one hit series, we found a correlation between activity and affinity. Mutant interaction studies suggest the inhibitors’ binding site. Conclusion: Surface plasmon resonance is a valuable technology in drug design, that has been used in this study to identify and evaluate σ70:core RNA polymerase inhibitors.

The presence of free carboxylic acid group in majority of non-steroidal anti-inflammatory drug (NSAIDs) is responsible from GI irritation. Coupling of the appropriate NSAIDs (diclofenac, naproxen, dexibuprofen and meclofenamic acid) 1–4, respectively with the appropriate amino acid ester 5 using dicyclohexylcarbodiimide afforded prodrugs 6–13. The structures of the prodrugs were verified based on spectral data. Chemical hydrolysis studies performed in three different non enzymatic buffer solutions at pH 1.2, 5.5 and 7.4, as well as in 80% human plasma and 10% rat liver homogenate using HPLC indicate no conversion of prodrugs to their respective NSAID in the studied buffers, while they underwent a reasonable plasma and rat liver homogenate hydrolysis. Furthermore, ulcerogenicity of prodrugs 9 and 12 were studied and results revealed no gastro-ulcerogenic effects.NULL

Square wave adsorptive stripping voltammetric (SQWASV) method has been utilized to confirm and elucidate the possible complexation reaction between pantoprazole sodium and cobalt as a transition metal in Britton- Robinson buffer (pH=7.0). The current signal due to the oxidation process was a function of the amount of pantoprazole sodium, pH of the medium, cobalt concentration and accumulation time at the electrode surface. The oxidation peak current has varied linearly with the concentration over the range of 0.1–9.0 nM. The limit of detection was found to be 0.04 nM. The validity of the method was successfully applied for the determination of pantoprazole sodium in pharmaceutical formulations with a pharmacokinetic study in rabbit plasma. The simplicity, rapidity, sensitivity and selectivity of this method make it a very attractive alternative to the other existing methods in the quality control laboratories.