Current Medicinal Chemistry - Volume 30, Issue 4, 2023

Background: Benzoxazine is one of the most important privileged scaffolds in medicinal chemistry. Compounds bearing benzoxazine moiety usually have a variety of biological activities, such as anti-inflammatory, anti-microbial, anti-tuberculosis, anti- oxidant and anti-cancer activities. The fascinating bioactivity profile of benzoxazine scaffold in various fields has prompted medicinal chemists to design and discover novel benzoxazine derivatives as potential therapeutic candidates with the desired biological properties. Objective: This review aimed to provide a comprehensive elucidation on the recent advances of benzoxazine derivatives in medicinal chemistry. Methods: We have searched the recent literature about benzoxazine derivatives from the online resources and databases, such as PubMed, SciFinder and Google Scholar. Results: Many benzoxazine derivatives with a wide range of bioactivities, such as anti- microbial, anti-cancer, anti-tuberculosis, anti-oxidant and anti-inflammatory, were summed up. Many compounds displayed good biological activities. Conclusion: Benzoxazine is a versatile structure and building block in medicinal chemistry. Benzoxazine derivatives have gained considerable attention from medicinal chemists due to their various pharmacological properties and multiple modification sites. This review might help medicinal chemists to seek new drug candidates with better bioactivities and pharmacokinetics properties.

The immune system's role in maintaining the health of the gastrointestinal (GI) system is like a double-edged sword. Simultaneously, it could reduce the risk of pathogen invasion by the inflammatory response. However, if regulated improperly, it could also propagate oncogenic signaling that transfers a normal cell into the malignant counterpart. Thus, several mechanisms have been proposed, such as the immune system could disturb the GI homeostasis and increase the survival and proliferative capacity of cells, leading to the formation of a wide range of malignancies. Among the endless list of these mechanisms, inflammatory responses are currently fascinating research areas, as this response regulation is by the gut microbiota. Given this, microbiota manipulation might be a convenient and efficient way to prevent GI cancer. Probiotics could potentially achieve this by overturning the milieu in favor of normal gut homeostasis. In addition to the safety of the use of probiotics, along with their potential ability to interact with immune system responses, these bacteria are also being analyzed from the perspective of dietary supplements. In the present review, we aimed to look into the mechanisms through which probiotics modulate immune response to stimulate anti-inflammatory responses and promote immune surveillance against neoplastic cells.

Sulfonamides constitute an important class of drugs, with many types of pharmacological agents possessing antibacterial, anti-carbonic anhydrase, anti-obesity, diuretic, hypoglycemic, antithyroid, antitumor, and anti-neuropathic pain activities. The sulfonamides are the compounds that have general formula R-SO2NHR', where the functional group is bound to aromatic, heterocycle, and aliphatic groups. The nature of the R and R' moiety is variable, starting with hydrogen and ranging to a variety of moieties incorporating organic compounds such as coumarin, isoxazole, tetrazole, pyrazole, pyrrole, and so many other pharmaceutical active scaffolds that lead to a considerable range of hybrids named as sulfonamide hybrids. Part A of this review presents the most recent advances in designing and developing two-component sulfonamide hybrids containing coumarin, indole, quinoline, isoquinoline, chalcone, pyrazole/pyrazoline, quinazoline, pyrimidine, thiazole, benzothiazole, and pyridine between 2015 and 2020. Specifically, the authors review the scientific reports on the synthesis and biological activity of this kind of hybrid agent.

Background and Objective: Studies on the association between blood fibrinogen levels and adverse outcomes in patients with acute ischemic stroke have produced controversial results. This meta-analysis aimed to examine the association of elevated fibrinogen levels with adverse outcomes in acute ischemic stroke patients. Methods: Two authors comprehensively searched the articles indexed in PubMed and Embase databases until December 31, 2021. All cohort studies that assessed the value of fibrinogen level in predicting poor functional outcomes or all-cause mortality in acute ischemic stroke patients were included. Results: Nine studies reporting on ten articles involving 16,998 patients met the inclusion criteria. For the highest versus lowest fibrinogen group, the pooled adjusted risk ratio (RR) was 1.48 (95% confidence intervals [CI] 1.17-1.87) for poor functional outcomes defined by the modified Rankin Scale ≥ 3. In addition, elevated fibrinogen was not significantly associated with an increased risk of all-cause mortality (RR 1.76; 95% CI 1.42-2.20). Subgroup analysis suggested that there was no clear association between elevated fibrinogen levels and PFO in younger acute ischemic stroke patients (RR 1.16; 95% CI 0.87-1.53). Conclusion: Elevated fibrinogen level at baseline is possibly an independent predictor of short-term poor functional outcome and long-term all-cause mortality, particularly in elderly acute ischemic stroke patients. Blood fibrinogen level may serve as a useful biomarker for risk classification of acute ischemic stroke patients.

Background: Cardiorenal syndromes (CRS), involving the heart-kidney cross-talk and the activation of neurohumoral and inflammatory pathways, are an entity characterized by high morbidity and mortality. Objective: To evaluate the prognostic role of risk factors and biomarkers in patients hospitalized for CRS. Methods: In this observational cohort study, 100 consecutive patients hospitalized for CRS were enrolled. Socio-demographic characteristics, personal medical history, and prior medication use were recorded upon admission, and echocardiography was performed. Moreover, an array of blood markers were measured. The endpoint of interest was a composite of death or dialysis dependence at discharge. Results: Patients were classified into two groups; Group 1 (N= 52): discharged being dialysis-independent, Group 2 (N=48): death/dialysis dependence at discharge. No significant differences were detected in baseline characteristics between the two groups. Group 2 patients used renin-angiotensin-aldosterone system blockers (RAASb) less often and more frequently presented with oliguria/anuria. Group 2 patients had significantly lower hemoglobin, serum albumin, and 25-hydroxy-vitamin D (25(OH)D). At the same time, serum phosphate, potassium, and parathyroid hormone (PTH) were significantly higher in Group 2 patients. In a multivariate regression analysis, lack of prior RAASb and lower 25(OH)D levels were independently associated with an increased risk of death or dialysis dependence at discharge. 25(OH)D/PTH ratio was the most accurate predictor of the composite endpoint (Sensitivity: 79.4%, Specificity: 70.4%). Conclusion: Lack of prior RAASb use, high PTH, low 25(OH)D levels, and low 25(OH) D/PTH ratio are associated with a poor prognosis in patients hospitalized for CRS.