Synthesis, spectral analysis, DFT calculations, biological potential and molecular docking studies of indole appended pyrazolo-triazine.

A series of novel 5-(3,5-disubstituted-1H-indol-2-yl)-2,3-dimethyl-1-phenyl-2,6-dihydro-1H-pyrazolo[4,3-e][1,2,4]triazines (3a-l) were synthesized in single step from 3,5-disubstituted indole-2-carbohydrazide and 4-aminoantipyrine under acidic conditions with excellent yields. The various spectroscopic methods were used to prove the formation of all these products. The compounds 3a, 3b, 3e, 3f, 3i and 3j exhibited excellent antibacterial and antifungal activities with an MIC value of 3.125 µg/ml against the tested pathogens and anti-tuberculosis inhibitory potential against M. tuberculosis which is equivalent to standard drug. The antidiabetic activity of the compounds 3a and 3b showed the maximum potential as glucosidase inhibitors with IC50 = 47.21 µg/ml and IC50 = 48.36 µg/ml, respectively. The physicochemical characteristics like ADMET, drug-likeness and bioactivity scores for these molecules were also disclosed. To comprehend the electronic behavior of compound 3a, density functional theory estimations at the DFT/B3LYP level via 6-31G++ (d, p) have been carried out to replicate the structure and geometry. The first-order hyperpolarizability calculation was used to calculate the nonlinear visual feature of compound 3a. The charge transfer interface among the structure is elucidated by the estimated HOMO-LUMO analysis. Further, molecular docking studies were carried out for synthesized compounds with human maltase-glucoamylase (PDB: 2QMJ).

An insight into therapeutic efficacy of heterocycles as histone-modifying enzyme inhibitors that targets cancer epigenetic pathways.

Histone-modifying enzymes are the key regulators involved in the post-translational modification of histone and non-histone. These enzymes are responsible for the epigenetic control of cellular functions. However, deregulation of the activity of these enzymes results in uncontrolled disorders such as cancer and inflammatory and neurological diseases. The study includes histone acetyltransferases, deacetylases, methyl transferases, demethylases, DNA methyl transferases, and their potent inhibitors which are in a clinical trial and used as medicinal drugs. The present review covers the heterocycles as target-specific inhibitors of histone-modifying enzyme, more specifically histone acetyltransferases. This review also confers more recent reports on heterocycles as potential HAT inhibitors covered from 2016 to 2022 and future perspectives of these heterocycles in epigenetic therapy.

Therapeutic potential of pyrrole and pyrrolidine analogs: an update.

The chemistry of nitrogen-containing heterocyclic compound pyrrole and pyrrolidine has been a versatile field of study for a long time for its diverse biological and medicinal importance. Biomolecules such as chlorophyll, hemoglobin, myoglobin, and cytochrome are naturally occurring metal complexes of pyrrole. These metal complexes play a vital role in a living system like photosynthesis, oxygen carrier, as well storage, and redox cycling reactions. Apart from this, many medicinal drugs are derived from either pyrrole, pyrrolidine, or by its fused analogs. This review mainly focuses on the therapeutic potential of pyrrole, pyrrolidine, and its fused analogs, more specifically anticancer, anti-inflammatory, antiviral, and antituberculosis. Further, this review summarizes more recent reports on the pyrrole, pyrrolidine analogs, and their biological potential.

A comprehensive insight on the biological potential of embelin and its derivatives.

Naturally occurring bioactive molecules are known for their diverse biological applications such as antimicrobial, anticancer, anti-inflammatory, and analgesic activities. Also, some of the natural products act as medicinal drugs. Further, bioactive cell-permeable molecule embelin has been reported for its diverse biological activities such as antimalarial, anticancer, and anti-inflammatory in the literature. With the continuation of our research work on biologically active molecules, based on structural activity relationship and docking studies of embelin and its derivatives, we have reported target-specific anticancer and antimalarial activities of embelin and its analogs. Also, it has been reported in many recent research articles that embelin and its derivatives are known to possess medicinal properties. This review mainly highlights recent reports on broad-spectrum biological activities of the embelin and its analogs to date.

Biological markers of cardiac damage are not related to measures of cardiac systolic and diastolic function using cardiovascular magnetic resonance and echocardiography after an acute bout of prolonged endurance exercise.

OBJECTIVES: Seventeen male participants (mean (SD) (range): age 33.5 (6.5) years (46-26 years), body mass 80 (9.2) kg (100-63 kg), height 1.81 (0.06) m (1.93- 1.70 m)) ran a marathon to investigate the relationship between systolic function (using cardiac magnetic resonance (CMR)) and diastolic function (using echocardiography) against biomarkers of cardiac damage. METHODS: Echocardiographic and cardiac troponin I (cTnI)/N-terminal pro-B-type natriuretic peptide (NTproBNP) data were collected 24 h premarathon, immediately postmarathon and 6 h postmarathon. CMR data were collected 24 h premarathon and at 6 h postmarathon. RESULTS: Body mass was significantly reduced postmarathon (80 (9.2) vs 78.8 (8.6) kg; p<0.001). There was a significant E/A reduction postmarathon (1.11 (0.34) vs 1.72 (0.44); p<0.05) that remained depressed 6 h postmarathon (1.49 (0.43); p<0.05). CMR demonstrated left ventricular end-diastolic and end-systolic volumes were reduced postmarathon, with a preserved stroke volume. Left ventricular ejection fraction 6 h postmarathon significantly increased (64.4% (4.2%) vs 67.4% (5%); p<0.05). There were significant elevations in cTnI (0.00 vs 0.04 (0.03) µg/l; p<0.05) and NTproBNP (37.4 (24.15) ng/l vs 59.34 (43.3) ng/l; p<0.05) immediately postmarathon. Eight runners had cTnI elevations immediately postmarathon above acute myocardial infarction cutoff levels (≥0.03 µg/l). No correlations between cTnI/NTproBNP and measures of diastolic function (E, A, E/A, isovolumic relaxation time, E deceleration time and E/E') or measures of systolic function (stroke volume or ejection fraction) were observed immediately postmarathon or 6 h postmarathon. CONCLUSIONS: Biomarkers of cardiac damage after prolonged exercise are not associated with either systolic or diastolic functional measures.

Cardiovascular function and the veteran athlete.

The cardiovascular benefits of exercise are well known. In contrast, the impact of lifelong endurance exercise is less well understood. Long-term high-intensity endurance exercise is associated with changes in cardiac morphology together with electrocardiographic alterations that are believed to be physiologic in nature. Recent data however has suggested a number of deleterious adaptive changes in cardiac structure, function and electrical activity, together with peripheral and cerebral vascular structure and function. This review serves to detail knowledge in relation to; (1) Cardiac structure and function in veteran endurance athletes focusing on the differentiation of physiological and pathological changes in cardiac remodelling; (2) Cardiac electrical activity and the veteran endurance athlete with attention to arrhythmias, the substrate for arrhythmia generation and the clinical significance of such arrhythmias; (3) Peripheral and cerebral vascular structure and function in ageing and endurance-trained individuals; and (4) directions for future research.

A successful case of repeat thrombolysis in acute prosthetic valve thrombosis.

Acute heart failure is an important presentation in the Acute Medical Unit. We describe a case of successful repeat thrombolysis in an elderly woman presenting as an emergency with severe pulmonary oedema, due to acute prosthetic mitral valve thrombosis. The diagnostic imaging and therapeutic modalities available are also described.This case highlights the need for acute physicians to consider prosthetic valve thrombosis in the differential for patients with metallic heart valves who present with acute heart failure or cardiogenic shock.

Efficacy of personal symptom and family history questionnaires when screening for inherited cardiac pathologies: the role of electrocardiography.

AIMS: This study sought to confirm the efficacy of using resting 12-lead ECG alongside personal symptom and family history questionnaires and physical examination when screening for diseases with the potential to cause sudden cardiac death in the young. METHODS AND RESULTS: 1074 national and international junior athletes (mean age 15.8 (SD 0.7) years, range 10 to 27) and 1646 physically active schoolchildren (16.1 (SD 2.1) years, range 14 to 20) were screened using personal and family history questionnaires, physical examination and resting 12-lead ECG. Nine participants with a positive diagnosis of a disease associated with sudden cardiac death were identified. None of the participants diagnosed with a disease associated with sudden cardiac death were symptomatic or had a family history of note. CONCLUSION: Family history and personal symptom questionnaires alone are inadequate to identify people with diseases associated with sudden cardiac death. Use of the 12-lead ECG is essential when screening for cardiac pathology in the young.

Physiological left ventricular hypertrophy or hypertrophic cardiomyopathy in an elite adolescent athlete: role of detraining in resolving the clinical dilemma.

The differentiation of physiological left ventricular hypertrophy (LVH) from hypertrophic cardiomyopathy (HCM) can prove challenging for even the most experienced cardiologists. The case is presented of a 17 year old elite swimmer who had electrocardiographic and echocardiographic features that were highly suggestive of HCM. However, indices of diastolic function were normal and cardiopulmonary exercise testing revealed high peak oxygen consumption in keeping with physiological LVH. To resolve the diagnostic dilemma, the patient underwent detraining for eight weeks, after which, there was complete resolution of the changes seen on electrocardiogram and echocardiogram, indicating physiological LVH rather than HCM.