Novel 3-(substitutedbenzylideneamino)-5-methyl-1H-pyrazol-1-yl)(phenyl)methanone Derivatives Against Gram-positive, Gram-negative and fungal pathogenic strains

          A series of novel3-(substitutedbenzylideneamino)-5-methyl-1H-pyrazol-1-yl)(phenyl) methanone P1-12 derivatives were synthesized. The chemical structures of the compounds were proved by means of their IR, 1H-NMR, mass spectroscopic data and elemental analyses. The results showed that most of the synthesized compounds exhibited significant anti-bacterial and anti-fungal activities. Among the synthesized compounds P2, P5, P8, and P9 exhibited most potent in vitro antimicrobial activity. On the basis of the microbial results, further  insight  into  the  structural  requirements  for  targeting  pyrazol-1-yl)(phenyl) methanone to develop potential new agents to combat treatment of pathogenic strains

6-(substitutedbenzylidene)-2-methylthiazolo[2,3-b]oxazol-5(6H)-one Derivatives: New Class of Antihyperglycemic Agent

The novel compounds have been prepared in order to improve the pharmacological proï¬les of antihyperglycemic activity. In the present paper, series of 6-(substitutedbenzylidene)-2-methylthiazolo[2,3-b]oxazol-5(6H)-one O1-12 were tested against hyperglycemia. Their antihyperglycemic activity was evaluated by Streptozotocin (STZ) and Sucrose-loaded (SLM) model. The results of studies indicate that, among the compounds O1, O6, O10, O12, O8, and O3 displayed signiï¬cant reduction in blood glucose level in streptozotocin and sucrose loaded rat models. The purity of the synthesized compounds was characterized by means of IR, 1H-NMR, mass spectral and elemental analysis.Â

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Nephroprotective potential of Graptophyllum pictum against renal injury induced by gentamicin

Objective(s):To evaluate the effect of Graptophyllum pictum on lipid peroxidation and tissue antioxidant enzymes in liver and kidney of gentamicin induced nephrotoxic rats. Materials and Methods: Animals were grouped into 6: Group 1 received gum acacia, Group 2 received G. pictum ethanol extract (300 mg/kg), Group 3 received gentamicin, Groups 4, 5, 6 received gentamicin along with G. pictum at 300, 150, 75 mg/kg, respectively. Nephroprotective activity was evaluated by measuring thiobarbituric acid-reactive substances (TBARS), biochemical markers  Glutathione (GSH), Glutathione-S Transferase(GST), Superoxide dismutase (SOD), Catalase (CAT), serum urea and creatinine levels. Results: Results obtained showed that gentamicin induced nephrotoxic rats exhibited lower activities of biochemical markers and raised levels of TBARS, serum creatinine and urea. Remarkably, after treatment with G. pictum extract, anomalous levels of biochemical markers, lipid peroxidation and serum creatinine were returned to normal. Conclusion: The results propose that G. pictum has nephroprotective effects, and can be a promising natural source against gentamicin induced nephrotoxicity

Synthesis, in vitro anticancer and antioxidant activity of thiadiazole substituted thiazolidin-4-ones

A series of novel 5-alkyl/aryl thiadiazole substituted thiazolidin-4-ones were synthesized by a two-step process. In the first step, 5-alkyl/aryl substituted 2-amino-thiadiazoles were synthesized, which on reaction with substituted aromatic aldehydes and thioglycolic acid in presence of dicyclohexylcarbodiimide afforded thiazolidin-4-ones. All compounds were synthesized in fairly good yields and their structures were confirmed by spectral and physical data. The title compounds were screened for in vitro anti-proliferative activity on human breast adenocarcinoma cells (MCF-7) by the MTT assay. Most derivatives showed an IC50 less than 150 µmol L–1. Among the compounds tested, 2-(2-nitrophenyl)-3-(5-methyl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3f), 2-(3-fluorophenyl)-3-(5-methyl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3b), and 2-(4-chlorophenyl)-3-(5-methyl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3c) were found to be the most active derivatives with IC50 values of 46.34, 66.84, and 60.71 µmol L–1, respectively. Antioxidant studies of all synthesized compounds were carried out using diphenylpicrylhydrazyl assay. Among the compounds tested, 2-phenyl-3-(5-styryl-1,3,4-thiadiazol-2-yl)-thiazolidin-4-one (3s) elicited superior antioxidant activity with IC50 of 161.93 µmol L–1

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

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