Cardiovascular & hematological agents in medicinal chemistry最新文献

Background: Arterial thrombosis is one of the most significant healthcare concerns in the world. Echinochrome A (Ech-A) is a natural quinone pigment isolated from sea urchins. It has a variety of medicinal values associated with its antioxidant, anticancer, antiviral, anti-diabetic, and cardio-protective activities.

Objective: The current study aims to investigate the effect and mechanism of Ech-A to inhibit thrombus formation induced by ferric chloride in rats.

Methods: Twenty-four rats were assigned into four groups (n= 6); sham and thrombotic model groups were orally administered 2% DMSO, while the other groups were treated with two dosages of Ech-A (1 and 10 mg/kg, body weight). After seven days of administration, all groups were exposed to 50% ferric chloride for 10 min, except the sham group exposure to normal saline.

Results: The molecular docking showed the free binding energies of Ech-A and vitamin K (Vit. K) with Vit. K epoxide reductase were -8.5 and -9.8 kcal/mol, which confirm the antithrombotic activity of Ech-A. The oral administration of Ech-A caused a significant increase in partial thromboplastin time, prothrombin time, clotting time, platelet count, fibrinogen levels, factor VIII, glutathione reduced, catalase, nitric oxide, and glutathione S-transferase. While white blood cells count, calcium level, and malondialdehyde concentration significantly decreased. The histological examination revealed a definite improvement in the carotid and cardiac tissues in the Ech-A groups.

Conclusion: The study results showed that Ech-A prevented thrombosis by several mechanisms, including chelating calcium ions, increasing the NO concentration, suppressing oxidative stress, and antagonizing Vit. K.

Background: Premature menopause (PM) is defined as the end of ovulation before the age of 40 years, a condition commonly referred to as primary ovarian insufficiency. It has been shown there is an association between early menopause and a high risk of cardiovascular disease.

Aim: This study aimed to evaluate the effect of genetic polymorphisms related to premature menopause on cardio-metabolic disorders Objective: We aimed to investigate the single nucleotide polymorphisms associated with PM and the risk of cardio-metabolic disorders in the MASHAD cohort study.

Methods: In this cross-sectional study, a total of 117 women with PM were recruited and compared with 183 healthy women. All participants were assessed for anthropometric indices and genotyped for eight selected polymorphisms within seven different genes.

Results: A significant difference was observed in physical activity level (PAL) between the groups. Individuals with rs4806660 CC genotype had a 3.63-fold increased risk of metabolic syndrome. Moreover, individuals with a TT genotype of the rs2303369 polymorphism had a 3.11-- fold increased risk of obesity.

Conclusion: Our findings showed that genetic variations are risk factors related to cardio- metabolic disorders in women with premature menopause.

Background: venous thromboembolism (VTE) prophylaxis is crucial for reducing the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE). This network metaanalysis was carried out to determine the most effective intervention among selective Xa inhibitors and low molecular weight heparins (LMWHs) for perioperative surgical thromboprophylaxis in major abdominal, pelvic, lumbar spine, and lower limb surgeries.

Methods: A systematic literature search was conducted for randomized controlled trials (RCTs) comparing selective factor Xa inhibitors, LMWHs, and placebo as thromboprophylaxis agents in major abdominal, pelvic, lumbar spine, and lower limb surgeries. A Bayesian network metaanalysis was performed to compare all interventions for the risk of developing DVT, VTE, major VTE, total bleeding, and major bleeding. The surface under the cumulative ranking curves was used to rank all interventions.

Results: Of 1788 retrieved references, 42 RCTs comparing 11 anticoagulants were included. As compared to enoxaparin, the risk of DVT was significantly reduced in patients treated with fondaparinux [RR: 0.53 (95% CrI: 0.31, 0.93)] and rivaroxaban [RR: 0.42 (95% CrI: 0.27, 0.64)]; VTE in patients treated with bemiparin [RR: 0.09 (95% CrI: 0, 0.7)], edoxaban [RR: 0.43 (95% CrI: 0.18, 0.96)], fondaparinux [RR: 0.55 (95% CrI: 0.34, 0.91)] and rivaroxaban [RR: 0.56 (95% CrI: 0.34, 0.85)]; major VTE in patients treated with rivaroxaban [RR: 0.26 (95% CrI: 0.11, 0.6)]. According to the surface under the cumulative ranking curves (SUCRA) value, fondaparinux and bemiparin increase the risk of serious bleeding more than other factor Xa inhibitors and LMWHs.

Conclusion: Rivaroxaban, fondaparinux, edoxaban, and bemiparin are superior perioperative thromboprophylaxis agents than enoxaparin in major surgeries. Fondaparinux and bemiparin have shown the highest risk of major bleeding compared to other factor Xa inhibitors and LMWHs.

Iron Deficiency (ID) is common in patients with cardiovascular disease. More than 64 million patients are suffering from chronic heart failure. The prevalence of iron deficiency increases with the severity of cardiac and renal dysfunction and is probably more common amongst women.

Aim: This review article discusses multifactorial pathophysiology, the relationship between clinical characteristics, functional and absolute ID, and the advantages of medicinal intervention in chronic heart failure (CHF). It also covers how iron shortage affects other body parts.

Approach: The most recent publications that included substantial scientific data on the connection between CHF and ID, with or without anaemia, were selected.

Discussion: Complex physiopathological interactions, including higher hepcidin levels, systemic inflammation, and activation of the renin-angiotensin-aldosterone system, have been identified in these patients. These mechanisms exacerbate the outcomes for patients by amplifying the severity of anemia, chronic heart failure (CHF), and Chronic kidney disease (CKD). Research in this area has been limited and has shown inconsistent findings. Still, it has also examined evidence-based treatment approaches and diagnostic guidelines, especially in relation to iron supplements and erythropoietin-stimulating medications.

Conclusion: Anemia is a frequent chronic heart failure consequence and a poor prognostic factor. We still don't completely understand the many complex causes of anemia. Iron deficiency screening is highly recommended for people with cardiac ailments because of its significance for their prognoses. Due to the paucity of research proving its effectiveness, the high incidence of unfavourable gastrointestinal side effects, and the prolonged length of time required for treatment to boost haemoglobin levels, an oral iron supplement is not advised for people with chronic heart failure. An insufficient amount of iron not only impacts the heart but also various other body components.

Background: Coronary collaterals are the feeding bridges between the main epicardial arteries, and research has shown that this collateral development plays a crucial role in myocardial performance, especially in patients with coronary artery disease. However, the evolution of these collaterals has not been fully explained.

Objective: In this study, we aimed to reveal the effect of CD31 on coronary collateral development.

Methods: As a result of coronary angiography performed in our clinic, 89 patients with coronary artery disease and 90 patients with normal coronary arteries were included in the study. Collateral development degrees were recorded from the angiographic images of the subjects. CD31 values were compared between the group with coronary artery disease and the control group. In addition, the coronary artery disease group was divided into subgroups according to the collateral development in terms of good collateral development and poor collateral development, and the factors that may affect the collateral development were tried to be determined.

Results: CD31 levels were significantly higher in the group with coronary artery disease compared to the control group (p <0.001). In addition, CD31 levels in the subgroup with good collateral were significantly higher than in the group with weak collateral (p <0.001). In the correlation analysis, a significant positive correlation was found between serum CD31 level and SYNTAX score, age, glucose, and rentrop grade. Multivariate logistic regression analysis showed CD31 to be an independent predictor of good coronary collateral development.

Conclusion: CD31, a marker of angiogenesis, may be involved in coronary collateral development.

Type 2 diabetes is characterized by elevated blood glucose levels, leading to an increased risk of cardiovascular diseases. Sodium butyrate, the sodium salt of the short-chain fatty acid butyric acid produced by gut microbiota fermentation, has shown promising effects on metabolic diseases, including type 2 diabetes and cardiovascular diseases. Sodium butyrate demonstrates anti-inflammatory, anti-oxidative, and lipid-lowering properties and can improve insulin sensitivity and reduce hepatic steatosis. In this review, we investigate how sodium butyrate influences cardiovascular complications of type 2 diabetes, including atherosclerosis (AS), heart failure (HF), hypertension, and angiogenesis. Moreover, we explore the pathophysiology of cardiovascular disease in type 2 diabetes, focusing on hyperglycemia, oxidative stress, inflammation, and genetic factors playing crucial roles. The review suggests that sodium butyrate can be a potential preventive and therapeutic agent for cardiovascular complications in individuals with type 2 diabetes.

Introduction: The drug discovery and development domain has witnessed remarkable advancements due to the integration of computational methods, particularly Computer-Aided Drug Design (CADD). Discovering and creating new drugs involves structural modifications to enhance their effectiveness and physical attributes. This frequently includes employing semisynthetic techniques to investigate structure-activity relationships thoroughly. Noticeable progress in molecular biology, computational chemistry, combinatorial chemistry, and highthroughput screening is steering transformative changes in the pharmaceutical industry.

Background: High blood pressure or hypertension, a significant health issue, elevates the chances of heart, kidney, and brain complications, among other health concerns. It's a leading cause of untimely mortality globally. Therefore, it is important to search for new antihypertensive compounds that have fewer side effects and higher therapeutic activity.

Methods: Following molecular docking of the pyridazine derivatives, compounds were subjected to In-silico ADMET analysis. Subsequently, a low molecular weight compound was synthesized. Among the synthesized compounds characterization procedures include TLC, FT-IR, 1HNMR, and LC-MS techniques.

Result: Compound 8 exhibited the most favorable molecular docking results with alpha A1 and beta 1 adrenergic receptors. Compounds 3, 5, and 6 fulfilled the essential ADMET criteria. Subsequently, Compounds 3, 4, and 5 underwent additional synthesis and characterization procedures, including TLC, FT-IR, 1H-NMR, and LC-MS techniques.

Conclusion: Similar behavior was observed in compounds 6, 8, 10, and 11, all violating Pfizer's 3/75 rules in terms of TPAS. Hydrazinolysis of these b-benzoyl propionic acids produced pyridazine, which was utilized in synthesizing pyridazine derivatives. TLC, FT-IR, 1HNMR, and LCMS have characterized the compounds.

Background: Warfarin is an effective anticoagulant but requires close International Normalized Ratio (INR) monitoring and may occasionally require correction of excessive anticoagulation. Current guidelines provide limited practical guidance on the administration of vitamin K for the management of supratherapeutic INR levels ≥ 5.0 in non-bleeding outpatients.

Objective: Based on expert consensus and guidelines, the Atrius Health Anticoagulation Management Services (AMS) has developed internal guidance for oral vitamin K use in highly selected populations. This study will describe the internal guidance for oral vitamin K use and present associated results and clinical outcomes.

Methods: Episodes with INR > 5.0 were included, with vitamin K considered for episodes with INR ≥ 6. Moreover, compelling indications and exclusions to select ideal patients for vitamin K intervention were also defined.

Results: Overall, episodes were managed conservatively; of the 246 collected episodes of excessive anticoagulation, in 18 episodes (7%), patients received vitamin K, and in 228 (93%) episodes, patients did not receive vitamin K. The mean index INR was 6.0 (range 5.0 - 10.5, SD 1.07), with nearly 57% of episodes achieving INR correction and 15% of episodes developing INR overcorrection. High thrombotic risk patients, regardless of hemorrhagic risk, were less likely to receive vitamin K. Three episodes (1.2%) resulted in bleeding complications. No thrombotic complications occurred during the 30-day follow-up of the index INR value ≥ 5.0.

Conclusion: Our internal guidance is a novel, standardized approach that serves as a decision support tool for the management of warfarin-associated coagulopathy and vitamin K intervention using patient-specific characteristics and index INR values. This guidance may assist other anticoagulation management services with practical applications and require validation in a prospective clinical trial.

Background: Pulmonary Hypertension (PH) leads to changes in pulmonary vascular architecture, hypertrophy of the right ventricle, and heart failure. Sildenafil is a drug that can modulate PH by inducing smooth muscle relaxation and vasodilation.

Aims: To investigate the ability of sildenafil to alleviate the monocritaline (MCT)-induced PH in rats and to estimate the role and its effect on the atrial natriuretic peptide (ANP) levels.

Methods: 28 adult male rats were divided randomly into four groups: Group A (control group; n=7). Group B (MCT-treated group; n=7) was given a single dose of MCT 60 mg/kg subcutaneously. Group C (The reversal group; n=7) received a single dose of MCT 60 mg/kg subcutaneously for three weeks and then sildenafil at 50 mg/kg/day, given daily for another three weeks. Group D (The prevention group; n=7) simultaneously received a single dose of MCT 60 mg/kg subcutaneously and sildenafil daily at 50 mg/kg for three weeks.

Results: The animals in the prevention group showed a significant decrease in ANP levels compared to the reversal and MCT-treated groups. This decrease was associated with a significant reduction in the Fulton index ratio in the prevention group compared to the reversal group. The nitric oxide levels were also significantly higher in the reversal group than in the control group.

Conclusion: Preventive sildenafil treatment was associated with a significant decrease in ANP levels and reduced MCT-induced cardiac hypertrophy in rats.