Cardiovascular & hematological agents in medicinal chemistry最新文献

Background: Glioblastoma multiforme (GBM) is characterized by massive tumorinduced angiogenesis aiding tumorigenesis. Vascular endothelial growth factor A (VEGF-A) via VEGF receptor 2 (VEGFR-2) constitutes majorly to drive this process. Putting a halt to tumordriven angiogenesis is a major clinical challenge, and the blood-brain barrier (BBB) is the prime bottleneck in GBM treatment. Several phytochemicals show promising antiangiogenic activity across different models, but their ability to cross BBB remains unexplored.

Methods: We screened over 99 phytochemicals having anti-angiogenic properties reported in the literature and evaluated them for their BBB permeability, molecular interaction with VEGFR-2 domains, ECD2-3 (extracellular domains 2-3) and TKD (tyrosine kinase domain) at VEGF-A and ATP binding site, cell membrane permeability, and hepatotoxicity using in silico tools. Furthermore, the anti-angiogenic activity of predicted lead Trans-Chalcone (TC) was evaluated in the chick chorioallantoic membrane.

Results: Out of 99 phytochemicals, 35 showed an efficient ability to cross BBB with a probability score of > 0.8. Docking studies revealed 30 phytochemicals crossing benchmark binding affinity < -6.4 kcal/mol of TKD with the native ligand ATP alone. Out of 30 phytochemicals, 12 showed moderate to low hepatotoxicity, and 5 showed a violation of Lipinski's rule of five. Our in silico analysis predicted TC as a BBB permeable anti-angiogenic compound for use in GBM therapy. TC reduced vascularization in the CAM model, which was associated with the downregulation of VEGFR-2 transcript expression.

Conclusion: The present study showed TC to possess anti-angiogenic potential via the inhibition of VEGFR-2. In addition, the study predicted TC to cross BBB as well as a safe alternative for GBM therapy, which needs further investigation.

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: Nattokinase (NK) is a naturally occurring fibrinolytic protease enzyme obtained from the traditional Japanese food called Natto and has several uses in the pharmaceutical and medical industries. Nowadays, the most often used thrombolytic agent in the clinical field is NK, in part because it is less expensive than other thrombolytic medicines.

Objectives: The objective of this study is to investigate the screening, isolation and characterization of the NK enzyme-producing Bacillus strain from fermented Soya beans.

Methods: The sample of fermented soya beans were tested for the presence of fibrinolytic protease- producing bacteria, followed by the screening, extraction, characterization and clot lysis assays.

Results: A total of three isolates were screened for caseinolytic activities by casein hydrolysis assay. Out of those isolates, MRS18 was found to be potent in producing the enzyme proteinase. To determine the taxonomy and phylogeny of these isolates, biochemical and molecular characterization has been carried out. Bacillus amyloliquefaciens MRS18 has been found with the highest caseinolytic activity. The clot lysing ability of the potent strain Bacillus amyloliquefaciens was found to be 61.7% after 120 min, and on further purification, by ammonium sulphate precipitation method, the lysis percentage was found to be 656% after 120 min.

Conclusion: From the results of the present study, we concluded that Bacillus amyloliquefaciens isolated from the fermented soya beans produced an NK enzyme that exhibits immense potential to lyse blood clots.

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

Aims: The study aimed to investigate the antihypertensive activity of Scorzonera undulata ssp. deliciosa.

Background: Scorzonera undulata ssp deliciosa, locally known as "Guiz", is used in traditional medicine in Morocco as a diuretic and mainly against snake bites.

Objectives: This study investigated the possible antihypertensive effect of the aqueous extract of Scorzonera undulata (AESU).

Materials and methods: In the present study, the antihypertensive activity of AESU was tested in normotensive and hypertensive rats Results: The results indicated that AESU decreased the systolic, diastolic, and mean arterial blood pressure in hypertensive rats. The data revealed that AESU exerted its antihypertensive effect through vasodilatory properties. Interestingly, the study demonstrated that the vasorelaxation ability of AESU might be mediated through receptor-operated calcium channels (ROCCs). However, AESU dhad effect on inhibiting ACE-2.

Conclusion: The present study indicates the antihypertensive and vasorelaxant activities of AESU in hypertensive rats.

Background: Plants have been used for ages in traditional medicine, and it is exciting to perceive how recent research has recognized the bioactive compounds liable for their beneficial effects. Green synthesis of metal nanoparticles is a hastily emergent research area in nanotechnology. This study describes the synthesis of silver nanoparticles (AgNPs) using Coriandrum sativum and Murraya koenigii leaf extract and its thrombolytic activity.

Objective: The aim of the study was to determine the clot lysis activity of Coriandrum sativum and Murraya koenigii synthesized silver nanoparticles.

Methods: Leaves of Coriandrum sativum and Murraya koenigii were collected. Methanolic extraction of the plant sample was done through a Soxhlet extractor. The methanolic extract obtained from both the leaves was subjected to GC-MS analysis. The synthesized NPs from leaf extracts were monitored for analysis, where the typical X-ray diffraction pattern and its diffraction peaks were identified. 3D image of the NPs was analysed by Atomic Force Microscopy. The surface charge of nanoparticles was identified by Zeta potential. The Clot lysis activity of Coriandrum sativum and Murraya koenigii synthesized silver nanoparticles were analysed by the modified Holmstorm method.

Results: The thrombolytic property of the methanolic extract of plants Coriandrum sativum showed clot lysis activity at 2.5 mg/mL with 45.99% activity, and Murraya koenigii extract with 66.56% activity. The nanoparticles (Nps) from Coriandrum sativum showed clot lysis activity at 2.5 mg/mL with 58.29% activity, and NPs from Murraya koenigii with 54.04% activity. Coriandrum sativum in GC-MS exhibited 3 peaks, whereas Murraya koenigii extract showed five peaks with notable bioactive compounds.

Conclusion: These NPs were further used for biomedical applications after being fixed by an organic encapsulation agent. The present research reveals the usefulness of Coriandrum sativum and Murraya koenigii for the environmentally friendly manufacture of silver nanoparticles.

Background: Herbal remedies are used by 80% of the Asian population in primary health care as per WHO. According to current research, the herbal medicine market was valued at nearly USD 166 billion in 2021 and is expected to reach approximately USD 348 billion by 2028. Increased incidence of chronic conditions such as diabetes, asthma, coronary artery disease, osteoarthritis, has fueled the growing interest in traditional herbal and plant-derived treatments among researchers. In addition, rural communities in developing nations have renewed interest in herbal treatments due to lower cost and easy availability.

Objectives: Aim of the paper is to highlight the role of five of more commonly used herbal medicines that are Ginkgo biloba, Garlic, Flaxseed, Ginseng, Salvia miltiorrhiza in cardiovascular disorders.

Methods: A PubMed search was done using the keywords Herbal Medicine, Ginkgo biloba, Garlic, Flaxseed, Ginseng, Salvia miltiorrhiza. Articles which were available for free access were utilized. No formula inclusion or exclusion criteria was followed. A total of 42 papers were included for the study.

Conclusion: Although there have been encouraging outcomes with the use of these herbal medications, many of these products are poorly monitored and are yet to be studied in detail regarding their adverse effects. Moreover, these medicinal products are known to interact with various drugs. To compete with the expanding pharmaceutical industry, more medicinally helpful herbal items must be used and scientifically validated.

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) mediated by O6- methylguanine DNA methyltransferase (MGMT). 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.

Background: Beta-blockers are essential agents in the management of cardiovascular diseases, such as heart failure, acute myocardial infarction (MI), and cardiac arrhythmias. However, there are diurnal variations in the cardioprotective effects of the subgroups as a result of their different pharmacokinetic, pharmacodynamic, and pharmacogenetic profiles.

Objective: We aimed to compare metoprolol and bisoprolol in terms of electrocardiogram (ECG) outcomes.

Methods: A retrospective cross-sectional study was conducted at Prince Sultan Cardiac Center. The trial included 404 patients who met the inclusion criteria (204 in the metoprolol arm and 200 in the bisoprolol arm). Using case record forms that had already been created, information, such as patient demographics, medical histories, and treatment histories, was taken from their medical files. The most recent ECG records were also gathered. The ethical approval for this study was obtained from Qassim ethical committee (approval number: 45-44-902).

Results: There was no significant difference found between the patients in both arms in terms of baseline characteristics, age, or sex.

Conclusion: In this retrospective cross-sectional study, we have compared the effects of metoprolol and bisoprolol beta blockers on ECG changes. The findings have indicated no difference between metoprolol and bisoprolol groups in terms of all ECG readings, particularly PR/ms, QTC-ms, and ventricular rate. Further studies are required to confirm these findings.

Background: Type 2 diabetes has become a concern issue that affects the quality of life and can increase the risk of cardiac insufficiency elevating the threat to the life safety of patients. A recognized cause of cardiac insufficiency is diabetic cardiomyopathy, chronic hyperglycemia, and myocardial lipotoxicity which can reduce the myocardial contractile performance, and enhance the cardiomyocyte hypertrophy and interstitial fibrosis. The cause of diabetic cardiomyopathy is multi-factorial which includes oxidative stress, insulin resistance, inflammation, apoptosis, and autophagy. Recent clinical studies have suggested the dysbiosis of gut microbiota, secretion of metabolites, and their diffusion in to the host as to have direct detrimental effects on the cardiac contractility.

Material and methods: In the present paper, we have done in silico studies including molecular interaction of phytoconstituents of Tinospora cordifolia against reactive oxygen species producing proteins. Whereas, in vitro studies were conducted on H9C2 cardiac cells including cell morphological examination, level of reactive oxygen species, cell count-viability, apoptotic status, in the presence of high glucose, trimethylamine-n-oxide, and plant extracts which were determined through cell analyzer and microscopic assays.

Results: The treatment of high glucose and trimethylamine-n-oxide was found to be increase the cardiac stress approximately two fold by attenuating hypertrophic conditions, oxidative stress, and apoptosis in rat cardiomyocytes, and Tinospora cordifolia was found to be a cardioprotective agent.

Conclusion: Conclusively, our study has reported that the Indian medicinal plant Tinospora cordifolia has the ability to treat diabetic cardiomyopathy. Our study can open up a new herbal therapeutic strategy against diabetic cardiomyopathy.