Identification of potential drug candidates to treat gastritis and associated oxidative stress based on some novel 2-aryl-1H-naphtho[2,3-d]imidazole: synthesis, in vitro and in silico analysis.

To identify potential scaffolds to treat gastritis and oxidative stress, 2-aryl-1H-naphtho[2,3-d]imidazole derivatives (1-15) were synthesized. The synthesis was conveniently carried out by condensing 2,3-diaminonaphthalene with variously substituted aldehydes to yield 15 new 2-aryl-1H-naphtho[2,3-d]imidazole derivatives. Structures of all synthesized compounds were elucidated using MS and NMR spectroscopic techniques. Compounds containing an imidazole moiety have continued to spark interest in the field of medicinal chemistry due to their unique properties. In continuation of this statement, to further explore the biological potential of these types of compounds, newly synthesized imidazole derivatives were evaluated for their inhibitory potential against urease and antioxidant activities. Compounds 4 and 11 were identified as the most potent urease inhibitors in the series, with IC50 values of 34.2 ± 0.72 and 42.43 ± 0.65 µM, respectively. Compounds 1, 3, 6, 11, and 15, with EC50 values in the range of 37-75 µg ml-1, showed significant antioxidant activity. Molecular docking studies of the selected synthesized compounds 3, 4, 9, and 11 were also performed to determine their binding interaction with the jack bean urease. Through docking studies, it was revealed that all the compounds that showed good inhibitory potential against urease fit well within the protein's binding pocket. Furthermore, ADME analysis was carried out to explore the drug-likeness properties of the compounds. The findings of the present work revealed that compounds 4 and 11 could be better options to treat gastritis and associated oxidative stress.

Enhancement in spatial and recognition memory functions following long term oral administration of ginger extract in rats.

Ginger (Zingiber Officinale) is known over the centuries for its medicinal properties and has been used worldwide as health supplement and for treatment of several diseases. The purpose of this study was to evaluate the effects of whole ginger extract administration on spatial and recognition memory using experimental animal models. The antimicrobial properties of ginger extract against various pathogenic fungal and bacterial species were also examined. Aqueous extract of ginger at a dose of 500 mg/kg was orally administered to test rats and water was orally given to control rats for 6 weeks. Water Maze task (WM) was used to assess spatial memory and recognition memory of rats was evaluated by the Novel Object Recognition (NOR) task. Time spent with novel object was significantly increased in ginger treated rats as compared to control animals in novel object recognition task exhibiting enhanced recognition memory in ginger treated rats. Ginger treated rats exhibited significantly enhanced both short term memory and long term memory as evidenced by decrease in time to reach the hidden platform 1h and 24 h after training as compared to control rats. Short term memory functions of ginger treated rats were more enhanced than long term memory functions. Our findings suggest that ginger consumption may lead to an improvement in spatial and recognition memory. Significant activity of aqueous ginger extract was observed against pathogenic bacteria as well as fungal species. It is therefore suggested in this study that ginger extract can be used in microbial infections and as a memory enhancing drug in various memory disorders.

Antimicrobial and antioxidant screening of N¢-substituted sulphonyl and benzoyl derivatives of 4-Pyridine carboxylic acid hydrazide.

In this research program, the antibacterial, antifungal and antioxidant activities of six N'-substituted sulfonyl and benzoyl derivatives of lead molecule PCH were reported. Out of these compounds, sulphonyl derivatives 2,3 and benzoyl derivative 5 showed moderate to good activity against different strains of gram-positive and gram-negative bacteria including B. cereus, B. subtilis, B. thruingiensis and S. pyogenes, S. fecalis and E. coli ATCC 8739. Moreover, upon antifungal screening, the compound, N¢-[(2,4,6-trimethylbenzene) sulfonyl]pyridine-4-carbohydrazide possessed good antifungal activity against Candida species, a causative agent of systemic fungal infections. Antioxidant study demonstrated more than 50% inhibition in DPPH assay for sulphonyl derivative 2 indicating its potential as antioxidant while the other derivatives expressed low level of radical scavenging property.

Synergy between antibiotics and natural agents results in increased antimicrobial activity against Staphylococcus epidermidis.

INTRODUCTION: Staphylococcus epidermidis is one of the most frequent causes of biofilm-associated infections on indwelling medical devices. With the emergence of methicillin-resistant S. epidermidis (MRSE), there is an urgent need to discover novel active agents against a range of Gram-positive pathogens. We screened the clinical isolates of S. epidermidis for susceptibility/resistance against commonly prescribed antibiotics. Furthermore, we tested some natural agents alone and in combination with antibiotics to find possible synergistic antimicrobial effects. METHODOLOGY: S. epidermidis clinical isolates were screened for susceptibility/resistance against vancomycin, erythromycin, tetracycline, chloramphenicol, ampicillin, ofloxacin, cephalexin, and gentamicin using the Kirby-Bauer disk diffusion method. The antimicrobial potential of Camellia sinensis, Juglans regia, and Hippophae rhamnoides alone and in combination with antibiotics were examined using the disk diffusion method, where the antimicrobial potential activity was measured in terms of formation of zones of inhibition. RESULTS: Most S. epidermidis isolates were found to be resistant to one or more antibiotics. Gentamycin and ofloxacin were found to be the most effective antibiotics against S. epidermidis isolates. Extracts of Hippophae rhamnoides, Juglans regia, and Camellia sinensis were found to be equally effective against S. epidermidis isolates. In combination with antibiotics, these extracts exhibited appreciable synergistic activity; the highest synergistic activity was observed with erythromycin and cephalexin. In the case of cephalexin, a reversion in resistance was observed. CONCLUSIONS: The plant extracts used in the study exhibited additive and synergistic antibacterial activity against S. epidermidis, hence providing an effective alternative to deal with the problem of multidrug resistance.

Development of an in-house enzyme-linked immunosorbent assay based on surface whole cell antigen for diagnosis of Helicobacter pylori infection in patients with gastroduodenal ulcer disease.

Helicobacter pylori (H. pylori) is a causative agent of gastritis, gastroduodenal ulcers and gastric adenocarcinoma. More than 50% world population is colonized by H. pylori, which is closely related to the chronic gastritis and gastric ulcer infection. In this study, a total of 214 gastritis patient's serum samples were screened for anti-H. pylori IgG antibody. A 96-well plate coated with 20 µg/ml antigen and hundred-fold diluted patient's serum was allowed to react. After extensive washing with buffer, 1:2,500 diluted conjugated secondary antibody was added. Later substrate was added to observe positivity by measuring the intensity of color. Statistical analyses were performed, and p value of <0.01 was taken as significant; 84% male patients and 89% female patients, respectively, tested positive for H. pylori, while agewise distribution was 35-45 years males (40%) and 35-55 years females (52%) were found highest number of H. pylori infected patients. In-house ELISA based on surface whole cell antigen (wELISA) showed a sensitivity of 93%, specificity of 100%, accuracy 94% and κ value 0.86 with significant correlation R-0.77020; p < 0.0001. We conclude that H. pylori local isolates surface antigen was satisfactory for diagnosis as different parameters were adjusted according to the local H. pylori isolates. Fluctuations in serum antibody titer predict the variation in an individual's response of the host against H. pylori. In-house wELISA could provide a reliable and a clinically useful method for the diagnosis of H. pylori infection in patients of Karachi, Pakistan.

Antibacterial, Antifungal and antioxidant activities of some medicinal plants.

The purpose of this study was to evaluate the antibacterial, antifungal and antioxidant activities of medicinal plants. The antibacterial activity of methanolic extracts of three medicinal plants (Swertia chirata, Terminalia bellerica and Zanthoxylum armatum) were tested against Gentamicin (standard drug) on eleven gram positive and seventeen gram negative bacteria by agar well method. It was revealed that seven-gram negative and six gram positive bacterial species were inhibited by these plant extracts. Minimum inhibitory concentrations (MIC) of the extracts were determined by broth micro-dilution method. The significant MIC value of Swertia chirata was 20mg/ml against Serratia marcesens, Zanthoxylum armatum was 10 mg/ml against Aeromonas hydrophila and Terminali bellerica was 20mg/ml against Acinetobacter baumanii as well as Serratia marcesens. Antifungal screening was done for methanolic extracts of these plants by agar well method with the 6 saprophytic, 5 dermatophytic and 6 yeasts. In this case Griseofulvin was used as a standard. All saprophytes and dermatophytes were showed resistance by these plants extracts except Microsporum canis, which was inhibited by Z. armatum and S. chirata extracts. The significant MIC value of Zanthoxylum armatum was 10mg/ml against Microsporum canis and Swertia chirata was 10mg/ml against Candida tropicalis. The anti-oxidant study was performed by DPPH free radical scavenging assay using ascorbic acid as a reference standard. Significant antioxidant activities were observed by Swertia chirata and Zanthoxylum armatum at concentration 200µg/ml was 70% DPPH scavenging activity (EC50=937.5µg/ml) while Terminalia bellerica showed 55.6% DPPH scavenging activity (EC50=100µg/ml). This study has shown that these plants could provide potent antibacterial compounds and may possible preventive agents in ROS related ailments.