Norfloxacin derivatives as DNA gyrase and urease inhibitors: synthesis, biological evaluation and molecular docking.

Background: DNA gyrase and urease enzymes are important targets for the treatment of gastroenteritis, appendicitis, tuberculosis, urinary tract infections and Crohn's disease. Materials & methods: Esterification of norfloxacin was performed to enhance DNA gyrase and urease enzyme inhibition potential. Structure elucidation and chemical characterization were done through spectral (1H NMR, Fourier transform IR, 13C NMR) and carbon, hydrogen, nitrogen and sulfur analysis along with molecular docking. Results & conclusion: The majority of derivatives exhibited significant results but the 3e derivative showed maximum bactericidal, DPPH scavenging (96%), DNA gyrase and urease enzyme inhibitory activity with IC50 of 0.15 ± 0.24 and 1.14 ± 0.11 µM respectively which was further supported by molecular docking studies. So, the active derivatives can serve as a lead compound for the treatment of various pathological conditions.

Design, Synthesis, and Biological Evaluation of Dexibuprofen Derivatives as Novel Anti-Inflammatory, Antioxidant and Molecular Docking Studies.

Prodrugs of dexibuprofen having ester moieties instead of free carboxylic acid which involves in gastrointestinal side effects have been synthesized. Dexibuprofen acid was condensed with different alcohols/phenols to afford the ester prodrugs. All of the synthesized prodrugs were characterized by their physical attributes, elemental analysis, FT-IR, 1 H-NMR, and 13 C-NMR spectroscopy. The in vitro anti-inflammatory studies was done by chemiluminescence technique reflect prodrugs have been more potent, owing to the different chemical structures. Lipoxygenase enzyme inhibition assay was also assess and found compound DR7 with IC50 =19.8 µM), DR9 (IC50 =24.8 µM) and DR3 (IC50 =47.2 µM) as compared with Dexibuprofen (IC50 =156.6 µM). It was also evaluated for docking studies revealed that DR7 has found to be more potent anti-inflammatory against 5-LOX (3 V99) as well as analgesic against COX-II (5KIR) enzyme. Anti-oxidant activities were also performed, DR3 (86.9 %), DR5 (83.5 %), DR7 (93.9 %) and DR9 (87.4 %) were found to be more anti-oxidant as compared to (2S)-2-[4-(2-methylpropyl)phenyl]propanoic acid (52.7 %).

Synthesis, Characterization, and Biological Evaluation of 2-(N-((2'-(2H-tetrazole-5-yl)-[1,1'-biphenyl]-4yl)-methyl)-pentanamido)-3-methyl Butanoic Acid Derivatives.

This study aimed to evaluate 2-(N-((2'-(2H-tetrazole-5-yl)-[1,1'-biphenyl]-4yl)-methyl)-pentanamido)-3-methyl butanoic acid-based ester derivatives as a new class of angiotensin-II receptor antagonists. For this purpose, a series of compounds were synthesized using a variety of phenols. Their chemical characterization was established by FTIR, 1HNMR, and 13CNMR techniques. The biological activities including antioxidant potentials using the DPPH assay, the antihypertensive assay, the urease enzyme inhibition assay, and the antibacterial assay using agar well diffusion methods were performed. All the new compounds showed significant free radical scavenging potentials more than the parent drug while retaining antihypertensive potentials along with urease inhibition properties. However, the AV2 test compound was found to be the most potent against hypertension. Most of the synthesized analogs showed urease inhibitory actions. Molecular docking studies were performed for all the active analogs to decode the binding detail of the ligands with receptors of the enzyme's active site.

The effectiveness of routine physiotherapy with and without neuromobilization on pain and functional disability in patients with shoulder impingement syndrome; a randomized control clinical trial.

BACKGROUND: The objective of the study was to compare the effects of neuromobilization (NM) techniques and routine physiotherapy on pain and functional disability in patients having shoulder impingement syndrome (SIS). Present study was aimed to discover evidence based conservative and cost effective remedy on pain and functional disability. STUDY DESIGN: Single blinded randomized control clinical trial. METHODS: A total of 80 patients with SIS were randomly assigned into care and experimental groups (40 in each group). After the baseline assessment routine physiotherapy was executed on both groups, while NM was applied additionally to experimental group. Pain and functional disability score were evaluated by Visual Analogue Scale and University of California at Los Angeles rating score at baseline, 5th and 11th week. Differences in outcome between groups were evaluated with clinical improvement. RESULTS: The experimental group compared with care group at 11th week had lower mean pain score 2.15(1.66-2.64) vs 4.90(4.41-5.40); between group difference, 1.82; 95% (CI), - 2.38 to - 1.25; P < 0.001 and Partial ƞ2 = 0.33, similarly functional disability score 28.58(27.32-29.83) vs 20.10(18.84-21.36); between group difference,5.62; 95%CI, (4.32-6.92); P< 0.001 and Partial ƞ2 = 0.49 respectively. In experimental group NM was a more effective technique to reduce the pain severity and disability in SIS patients as compare to care group. CONCLUSION: Neuromobilization techniques in addition to routine physiotherapy were significantly effective for the treatment of SIS. TRIAL REGISTRATION: IRCT20190121042445N1 , Registered 19 February 2019.

The effectiveness of routine physiotherapy with and without neuromobilization in patients with shoulder impingement syndrome.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of neuromobilization (NM) on the pain and active forward flexion in participants with shoulder impingement syndrome (SIS). METHODS: A randomized control trial was conducted in Social Security Hospital, Gujranwala. The duration of study was September 2016 to March 2018. A sample of 80 participants was selected and allocated in to two groups using computer generator method in simple random sampling technique. Consent was taken from patients with SIS for this trial. At the first session, participants were randomly assigned to either control group (n=40) or experimental group (n=40). After the baseline assessment routine physiotherapy was executed for both groups, while NM was provided to experimental group. Pain and active forward flexion (AFF) were evaluated at baseline, 5th week and 11th week. The data were entered and analyzed using SPSS (version 22.0). RESULTS: The experimental group compared with control group at 11th week had lower mean pain score 2.15 (1.66-2.64) vs 4.90 (4.41-5.40); between group difference, 1.82; 95% confidence interval (CI), -2.38 to -1.25; P ˂0.001 and Partial ƞ2=0.33, similarly with AFF 147.13 (142.46-151.79) vs 123.45(118.79-128.11); between group difference ,19.35; 95% CI, (12.86-25.83); P ˂ 0.001 and Partial ƞ2=0.30. Over all pain and AFF were improved among experimental group relative to control group at 11th week. CONCLUSIONS: In an experimental setting, the delivery of neuromobilization led to significantly different outcomes in participants of SIS than in control group.

Zingiber officinale ameliorates allergic asthma via suppression of Th2-mediated immune response.

CONTEXT: Ginger has been used commonly in the traditional system of medicine for the treatment of respiratory disorders. OBJECTIVE: The present study investigates the immunosuppressive activity of ginger by using the mouse model of ovalbumin-induced allergic asthma. MATERIALS AND METHODS: Treatment with ethanol extract (500 mg/kg) and aqueous extract (720 mg/kg) of rhizomes, and methylprednisolone (5 mg/kg) was initiated 1 week after second sensitization of mice with ovalbumin and continued for 7 d. RT-PCR followed by gel electrophoresis and ELISA were used for the evaluation of mRNA expression levels and protein levels of Th2 type markers, respectively. Lung tissue histopathology was conducted by using H&E and PAS staining. RESULTS: We observed significant reduction in goblet cell hyperplasia (0.83 ± 0.17 and 1.0 ± 0.26), infiltration of inflammatory cells in airways (0.67 ± 0.33 and 1.0 ± 0.37), and edema with vascular congestion (1.0 ± 0.26 and 1.2 ± 0.17) by both ethanol and aqueous extracts, respectively. A highly significant reduction of total and differential count of eosinophils and neutrophils in BALF, and eosinophil count in blood were also observed. Both extracts significantly inhibited Th2-mediated immune response, which is evident by a decrease in mRNA expression levels of IL-4 and IL-5. Protein levels of IL-4 and IL-5 in BALF, along with total serum IgE levels, were also significantly suppressed by both extracts. DISCUSSION AND CONCLUSION: Our study validated the traditional use of ginger in respiratory disorders and suggests that ginger reduces allergic airway inflammation, possibly by the suppression of Th2-mediated immune response.

Suppressive effects of black seed oil on ovalbumin induced acute lung remodeling in E3 rats.

OBJECTIVE: Black seed oil (BSO) is widely used as a traditional medicine for asthma and other inflammatory diseases. The aim of this study is to evaluate the effects of BSO on ovalbumin (OVA) induced acute lung remodelling in E3 inbred rats. METHOD: Rats were divided into three groups; Control, OVA and BSO. The rats were intraperitoneally sensitised and challenged intranasally with OVA and treated intraperitoneally with pure BSO for seven days. The collagen deposition and other pathological alteration were determined by Masson's trichrome, PAS and HE staining. Activity of arginase, ornithine decarboxylase (ODC) and proline level was determined by spectrophotometry, and polyamine by HPLC. The mRNA expression of arginase І, endothelin1 (Edn1), matrix metallopeptidase 3 (MMP3) and growth factors was determined by real time RT-PCR. RESULTS: Massive inflammation and characteristics of lung remodelling including collagen deposition, goblet cell hyperplasia and proline level were observed in the lungs of OVA exposed rats. Administration of BSO in the OVA exposed rats suppressed the inflammatory cells infiltration, goblet cell hyperplasia and collagen deposition. The activity of total arginase and ODC; proline and polyamine level was decreased in the lung homogenate of BSO treated rats. Furthermore, BSO abrogated the mRNA expression of Edn1, MMP3, transforming growth factor beta (TGF-ß), fibroblast growth factor 2 (FGF2) and vascular epidermal growth factor (VEGF) in the lungs of OVA challenged rats. CONCLUSION: Administration of BSO significantly reduced the level of allergen induced lung remodelling. The effect of BSO on lung remodelling is probably mediated by the inhibition of arginase pathways and the expression of Edn1, MMP3 and growth factors. Our findings suggest that BSO might have useful implications in the treatment and future research into allergen-induced lung remodelling.

Black seed oil ameliorates allergic airway inflammation by inhibiting T-cell proliferation in rats.

The black seeds, from the Ranunculaceae family, have been traditionally used by various cultures as a natural remedy for several ailments. In this study, we examined the effect of black seed oil as an immunomodulator in a rat model of allergic airway inflammation. Rats sensitized to ovalbumin and challenged intranasally with ovalbumin to induce an allergic inflammatory response were compared to ovalbumin-sensitized, intranasally ovalbumin-exposed rats pretreated with intraperitoneally administered black seed oil and to control rats. The levels of IgE, IgG1 and ova-specific T-cell proliferation in spleen were measured by ELISA. The pro-inflammatory cytokine IL-4, IL-5, IL-6 and TGF-beta1 mRNA expression levels were measured by reverse transcription polymerase chain reaction. The intraperitoneal administration of black seed oil inhibited the Th2 type immune response in rats by preventing inflammatory cell infiltration and pathological lesions in the lungs. It significantly decreased the nitric oxide production in BALF, total serum IgE, IgG1 and OVA-specific IgG1 along with IL-4, IL-5, IL-6 and TGF-beta1 mRNA expression. Black seed oil treatment resulted in decreased T-cell response evident by lesser delayed type hypersensitivity and lower T-cell proliferation in spleen. In conclusion, black seed oil exhibited a significant reduction in all the markers of allergic inflammation mainly by inhibiting the delayed type hypersensitivity and T-cell proliferation. The data suggests that inhibition of T-cell response may be responsible for immunomodulatory effect of black seed oil in the rat model of allergic airway inflammation.