Cardiovascular & hematological agents in medicinal chemistry最新文献

Background: Cardiomyopathy is a global health crisis that affects people all over the world. Consequently, scientists felt compelled to look for and develop ever-more-powerful pharmaceuticals. For ATTR-CM, the only drug currently recommended by the European Society of Cardiology is Tafamidis.

Objectives: The primary aim of this review article is to understand the chemistry, pharmacodynamic, pharmacokinetic, and bio-analytical methods available for Tafamidis.

Methods: A systematic review of the existing resources was accomplished up to 2022, comprising existing studies forming the database covering the existing resources from Web of Science, ScienceDirect, and PubMed.

Results: The review was based on a systematic review of all the existing studies used to formulate the database. The study also illustrated the PRISMA design that systematically analyses the prevalent resources.

Conclusion: Minimal analytical techniques are observed for quantifying the Tafamidis and transthyretin kinetic stabiliser. Therapeutic, pharmacological, and analytical considerations for the novel drug Tafamidis are discussed in this review. Particular attention is paid to the many different analytical and bioanalytical methods currently available for estimating Tafamidis, and the need is highlighted to develop a straightforward, validated technique that meets green chemistry standards.

Background: Numerous complications, such as postoperative arrhythmia and stroke, have been observed following coronary artery bypass graft (CABG) surgery.

Aims: This study sought to examine the impact of aging on the incidence of post-coronary artery shunt complications.

Objectives: Aging is a physiological process experienced by every living cell, beginning early in development. Age plays a crucial role in determining postoperative complications, including those related to CABG.

Materials and methods: A retrospective analysis was conducted on 290 patients who underwent CABG at the Mordovian Republic Hospital between 2017 and 2021. The sample was divided into two age-based groups: the first group comprised 126 patients (mean age range: 55.21-60.00), and the second group included 163 patients (mean age range: 66.11-80.00). Statistical analyses employed in this study encompassed descriptive statistics, Chi-square test, T-test, one-way ANOVA test, ROC analysis, and Pearson correlation using Statistica 12 software.

Results: Elderly patients in the second group demonstrated a higher incidence of post-CABG arrhythmia (p < 0.012528). Moreover, the second group experienced markedly longer ICU and total hospitalization days following CABG, with p-values of less than 0.000000 and 0.000072, respectively. Notably, elderly individuals in the second group faced an increased risk of developing psychosis after CABG surgery (p < 0.007379). Furthermore, psychosis was found to be significantly associated with longer ICU hospitalization (p < 0.000140). Postoperative stroke occurred more frequently among the elderly (second group) with a p-value of less than 0.037736. Consequently, postoperative stroke was associated with extended ICU hospitalization (p < 0.000747). The usage of internal thoracic arteries (ITAs) was lower among the elderly (second group), with a p-value of less than 0.016145. Regarding correlations, a direct association was observed between age and ICU days, total hospitalization days, and the number of complications, with correlation coefficients (r) of 0.189046, 0.141415, and 0.138565, respectively.

Conclusion: Elderly individuals in the second group who undergo CABG face a greater risk of developing psychosis, arrhythmia, prolonged total and ICU hospitalization, and stroke. The presence of arrhythmia, which is commonly observed in patients aged 63 years and older, significantly affects total hospitalization days. The number of complications is influenced by age, cardiopulmonary bypass (CPB) time, aortic cross-clamp time, ICU hospitalization, and total hospitalization duration.

Background: Cardiovascular disease and diabetes mellitus are among the leading causes of mortality.

Objectives: Our study evaluated endothelial function in patients with arterial hypertension, coronary heart disease, and diabetes mellitus.

Aims: This study aimed to assess the degree of endothelial dysfunction in individuals with cardiovascular risk factors older than 55 years of age.

Materials and methods: A total of 112 patients were subdivided into three groups according to the existing disease; the first group consisted of 50 patients diagnosed with arterial hypertension (AH), the second group consisted of 30 patients with ischemic heart disease (IHD), and the third group included 20 patients with type 2 diabetes mellitus (DM). The control group included 12 practically healthy volunteers, comparable in age and sex. Exclusion criteria were age under 55 years, severe concomitant diseases in the acute phase or acute infectious diseases, and oncopathology. Considered factors of cardiovascular risk include dyslipidemia, elevated fasting blood glucose, hypertension, obesity, cigarette smoking, and heredity for CVD. Moreover, tests were conducted with the help of the device 'AngioScan-01' (LLC "AngioScan Electronics"). Endothelium-dependent vasodilation (EDV), the index of stiffness of the vascular wall (SI), and the atherogenic index (log (TG/HDL - C )) were evaluated. The analysis of the data obtained was carried out using the IBM SPSS Statistic program.

Results: In the control group, the atherogenic index was in the range of 3.34 (the normal is up to 3.5). The highest atherogenic index, 4.01, was observed in the DM group (differences with the control group are statistically significant). In the AH and IHD groups, the atherogenic index was 3.57 and 3.65, respectively. In the control group, the level of glycemia was 4.45 mmol/l. The highest level of fasting glucose was reported in the DM group, i.e., 6.7 mmol/l (differences with the control group were statistically significant). In the first and second groups, the fasting glucose level was 5.07 mmol/l and 5.08 mmol/l, respectively. In the control group, the mean EDV score was 2,056 ± 0.757 mm, and the lowest EDV in the DM group was 1.365 ± 0.413, but in the AH and IHD groups, it was also significantly reduced by 1.404 ± 0.440 and 1.377 ± 0.390, respectively. The stiffness index in the control group was 6.725 ± 0.776 m/s. In the DM group, this parameter was 8.258 ± 0.656 m/s; in the AH and IHD groups, it was 7.398 ± 1.330 m/s and 7.486 ± 0.816 m/s, respectively.

Conclusion: In conclusion, the study of endothelial function using non-invasive angioscan reflects the influence of risk factors on the vascular wall. The most severe endothelial dysfunction is expressed in patients with diabetes. The results of endothelium-dependent vasodilation and the vascular

Multidrug-resistant ESKAPE pathogens are the leading cause of hospital-acquired infections across the globe, posing challenges for clinicians. Random genetic mutations and constant exposure to antibiotics in healthcare settings result in strains resistant to commonly used antibiotics, creating life-threatening conditions. If the magic of "antibiotics" is to be sustained, a new class of antimicrobials against novel targets is urgently needed. This necessitates understanding and identifying novel biochemical pathways and bacterial virulence factors that can be targeted for therapeutic interventions. Keeping in view the unambiguous role of the kinome in bacterial survival and virulence, this review provides a survey of effector bacterial kinases involved in evading host immune responses and drug resistance. The formation of biofilms is a critical feature associated with the pathogenesis and survival of ESKAPE organisms in the hostile host milieu. Hence, kinases involved in the biofilm pathway are also elucidated for clinical relevance. In addition, endeavors in the development of therapeutics against ESKAPE kinases are also summarized to provide direction to researchers pursuing the field.

Background: Colorectal cancer is estimated to become the leading cause of cancer death worldwide. Since most of the available therapies affect vital organs such as heart and liver, herbal remedies as a substitute therapy have been reported in several evidence-based studies.

Objective: Medicinal plants exhibit a diverse range of bioactive elements known for their medicinal properties, such as anti-inflammatory, anticancer, antioxidant, and antimicrobial effects. Phytochemicals present in medicinal plants significantly trigger different signaling pathways, contributing to their therapeutic activities. This review covers a comprehensive summary of the therapeutic potential of an herbal diet in treating colorectal cancer and other ailments. Special attention will be given to exploring the interactions of medicinal plants with the microbiota and their associations with cancer pathways.

Conclusion: A medicinal plant rich in bioactive compounds is a therapeutic option for colorectal cancer and potent cardioprotective and hepatoprotective agents. These bioactive compounds have demonstrated the ability to impede the growth of cancerous cells and trigger apoptosis. Our findings suggest that pomegranate, garlic, soybean, olive, green tea, papaya, and grapes are potential medicinal plants for combating cancer and related side effects. Bioactive compounds can modulate the gut microbiota's metabolism, and short-chain fatty acid production shows cardioprotective effects and reduces the risk of colorectal cancer. Hence, it can be stated that the interaction between a medicinal plant-rich diet and the gut microbiota plays a crucial role in preventing colorectal cancer and cardiac arrest.

Introduction: Repurposing of drugs for their anticancer potential is gaining a lot of importance in drug discovery.

Aims: The present study aims to explore the potential of Simvastatin (SIM), a drug used in the treatment of high cholesterol, and Thymoquinone (Nigella Sativa) (THY) for its anti-cancer activity on breast cancer cell lines. Thymoquinone is reported to have many potential medicinal properties exhibiting antioxidant, antiinflammatory, anti-cancer, activities like inhibition of tissue growth and division.

Methods: In this analysis, we explored the inhibitory effects of the combination of Simvastatin ad Thymoquinone on two breast cancer cell lines viz MCF-7 and MDA-MB-231 cells. The combined effect of Simvastatin and Thymoquinone on Cell viability, Colony formation, Cell migration, and orientation of more programmed cell death in vitro was studied. Cell cycle arrest in the G2/M phase was concomitant with the combined effect of SIM and THY persuading apoptosis and generating reactive oxygen species (ROS).

Results: The cell cycle arrest with combined treatment was observed that only 1.8% and 1.1% cells gated in G2/M phase in MCF-7 & MDA-MB-231 cell. An increased apoptosis was observed when cells were treated in combination which was about 76.20% and 58.15% respectively for MCF-7 and MDA-MB-231 cells.

Conclusion: It was concluded that the combined effect of simvastatin and thymoquinone stimulates apoptosis in breast cancer cells.

Background and objectives: Hypercholesterolemia is one of the main risk factors for vascular thrombosis in individuals. Therefore, the use of statins is very effective in reducing cholesterol and can reduce the risk of thrombosis in these patients. Rosuvastatin, a member of the statin family which, inhibits cholesterol synthesis. Very few studies have been done in relation to how rosuvastatin can affect thrombosis. So, this research has been tried whether rosuvastatin can have an effect on coagulation factors and homocysteine as risk factors for thrombosis in hypercholesterolemia?

Methods: In this experimental study, 60 patients (30 men and 30 women with a mean age of 40- 70 years) diagnosed with hypercholesterolemia (cholesterol > 250 mg/dl) participated in this research. 30 patients were prescribed rosuvastatin (20 mg/day), and 30 patients were simultaneously taken placebo for three months. All parameters, including FVIII, FV, Fibrinogen, DDimer, plasma homocysteine level and lipid profile, were measured before and after treatment. All the results were statistically compared between the two groups.

Results: In patients who took rosuvastatin, the drug was able to significantly reduce the concentrations of total cholesterol, triglycerides, and low-density lipoprotein (LDL) (P < 0.001). Also, rosuvastatin was able to reduce the concentrations of homocysteine significantly, D-Dimer (P < 0.001), coagulation factor VIII and factor V (P < 0.05). In patients with hypercholesterolemia who took the placebo, did not affect the mentioned variables (P > 0.05).

Conclusion: According to the results, it seems that rosuvastatin may be able to reduce the risk of thrombosis in patients by affecting coagulation factors and homocysteine levels.

Despite intense research in the field of glioblastoma multiforme (GBM) therapeutics, the resistance against approved therapy remains an issue of concern. The resistance against the therapy is widely reported due to factors like clonal selection, involvement of multiple developmental pathways, and majorly defective mismatch repair (MMR) protein and functional O6- methylguanine DNA methyltransferase (MGMT) repair enzyme. Phytotherapy is one of the most effective alternatives to overcome resistance. It involves plant-based compounds, divided into several classes: alkaloids; phenols; terpenes; organosulfur compounds. The phytocompounds comprised in these classes are extracted or processed from certain plant sources. They can target various proteins of molecular pathways associated with the progression and survival of GBM. Phytocompounds have also shown promise as immunomodulatory agents and are being explored for immune checkpoint inhibition. Therefore, research and innovations are required to understand the mechanism of action of such phytocompounds against GBM to develop efficacious treatments for the same. This review gives insight into the potential of phytochemical-based therapeutic options for GBM treatment.

Obesity and cardiovascular diseases are major health problems worldwide, and weight loss is used as a treatment strategy to enhance various aspects. While there are many weight loss methods, one of the most effective is through a dietary approach. The ketogenic diet (KD), which is characterized by low carbohydrates and high levels of fat and/or protein, is used in obese patients as it is a promising treatment option for weight loss as well as for controlling the risk factors for cardiovascular diseases, as seen in its effects on cardio-metabolic outcomes, particularly in obesity, heart failure, and hypertension. In this review, we summarize the clinical evidence of the efficacy and safety of the KD in controlling risk factors for cardiovascular diseases and discuss the possible mechanisms of action based on recent evidence in understanding the influence of the KD at the cellular and molecular levels.