RESUMO
Acute myocardial infarction (AMI) is a significant global cause of mortality, necessitating the exploration of innovative treatments against the condition. Angiotensin receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor-neprilysin inhibitors (ARNIs) such as sacubitril/valsartan have demonstrated promise in managing acute heart failure (HF). However, despite favorable evidence from clinical trials for the use of sacubitril/valsartan in AMI, its overall efficacy remains a subject of debate. Hence, we conducted this review and meta-analysis, by adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and aligned with European Society of Cardiology recommendations, to compare sacubitril/valsartan with traditional ACEI/ARB treatments for AMI. We employed Review Manager 5.4 for statistical analysis, the Risk of Bias Tool 2.0 was utilized for quality assessment, and publication bias was assessed using a funnel plot. A p-value <0.05 was considered statistically significant. Eight randomized controlled trials (RCTs) were included in this meta-analysis. Our findings revealed that participants treated with sacubitril experienced significantly improved outcomes in terms of HF (OR=0.79; 95% CI: 0.66-0.95; p=0.01; I2=23%), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (MD = -1.58; 95% CI: -1.78 to -1.37, p<0.00001; I2=97%), and major adverse cardiovascular events (MACE) (OR=0.84; 95% CI: 0.72-0.99; p=0.03; I2=44%). However, left ventricular ejection fraction (LVEF) (MD=3.68; 95% CI: 3.35-4.01, p<0.00001; I2=71%) showed greater improvement in the control group compared to the experimental group. Our meta-analysis suggests that sacubitril offers a favorable balance between safety and effectiveness. Sacubitril significantly improved outcomes in terms of HF, MACE, and NT-proBNP levels when compared to the control group. However, improvement in LVEF was notably higher in the control group over the sacubitril/valsartan group.
RESUMO
A series of flavonoid derivatives, flavones (F1-F3) and flavonols (OF1-OF3) were synthesized. Their structures were confirmed through various spectroscopic techniques and elemental analysis. These were then tested for cytotoxic activity against mouse fibroblast (NIH 3T3), human endothelial cervical (HeLa) and breast (MCF7) cell lines in vitro by MTT assay. The flavonol series showed prominent potentials than the flavones. The compound OF2 in flavonols exhibited greater potentials MCF7 cell with IC50 value of 0.96µM and OF3 has 1.04µM. In contrast, the OF3 exhibited higher activity against HeLa cell with IC50 value of 0.51µM and OF2 has 1.06µM. The compounds OF2 and OF3 exhibited activity against mouse fibroblast (NIH 3T3) cell with IC50 values 2.48 and 1.24µM. The OF1 was found to be moderate to inactive against all cells. Cytotoxic screening of the tested flavones, F1 to F3 were also active against all cells but the activity was less in comparison to flavonol series of compounds suggestion the possible involvement of hydroxyl (OH) at position 3 in case of flavonols. These results indicated a cheering scaffold that may lead to innovation of potent anti-breast cancer activity.
