Mini reviews in medicinal chemistry最新文献

Background and aims: Diabetic nephropathy (DN) is an important complication of diabetes, leading to end-stage renal disease (ESRD) worldwide. This review aimed to explore the role of the renin-angiotensin system (RAS) in DN, highlighting current treatments and emerging therapeutic perspectives.

Methods: We conducted a narrative review of the literature up to March 2024, focusing on the classical and alternative RAS axes, their implications in DN, and novel therapeutic approaches. Data were sourced from Scopus, PubMed, Scielo, and Cochrane databases.

Results: The classical RAS axis, involving angiotensin-converting enzyme (ACE), Angiotensin II (Ang II), and the AT1 receptor, promotes vasoconstriction, sodium retention, and fibrosis in DN. Hyperglycemia-induced Ang II increases oxidative stress, contributing to glomerular hyperfiltration and kidney damage. Current treatments include ACE inhibitors and angiotensin receptor blockers (ARBs), which reduce blood pressure and proteinuria, delaying DN progression. In contrast, the alternative RAS axis, featuring ACE2, Ang-(1-7), and the Mas receptor, offers renoprotective effects by counteracting Ang II actions. Ang-(1-7) reduces inflammation, fibrosis, and podocyte apoptosis. ACE2 activators, Ang-(1-7), and Mas receptor agonists show promise in preclinical studies, reducing glomerular fibrosis and improving renal function. Ang-(1-9) and alamandine may also hold potential in future treatments. Emerging therapies, such as the SGLT2 inhibitors, also demonstrate benefits in reducing DN progression.

Conclusion: While ACE inhibitors, ARBs, and SGLT2 inhibitors remain central to DN management, the ACE2-Ang-(1-7)-Mas axis presents a promising therapeutic target. Future research should focus on translating preclinical findings into clinical applications, potentially improving DN treatment.

Luminescent Lanthanide (III) (Ln(III)) bioprobes (LLBs) have been extensively used in the last two decades as intracellular molecular probes in bio-imaging for the efficient revelation of analytes, to signal intracellular events (enzymes/protein activity, antigen-antibody interaction), target specific organelles, and determine parameters of particular biophysical interest, to gain important insights on pathologies or diseases. The choice of using a luminescent Ln(III) coordination compound with respect to a common organic fluorophore is intimately connected to how their photophysical sensitization (antenna effect) can be finely tuned and especially triggered to respond (even quantitatively) to a certain biophysical event, condition or analyte. While there are other reviews focused on how to design chromophoric ligands for an efficient sensitization of Ln(III) ions, both in the visible and NIR region, this review is application-driven: it is a small collection of particularly interesting examples where the LLB's emissive information is acquired by imaging the emission intensity and/or the fluorescence lifetime (fluorescence lifetime imaging microscopy, FLIM).

Most natural products in nature have broad but not exceedingly good biological activities. The pyrazole structure has been introduced into natural products due to its suitability for various synthetic methods and its broad pharmacological activities. This article provides a detailed introduction to the anti-inflammatory, antibacterial, antifungal, antiviral, and anti-Alzheimer disease activities of pyrazole-modified natural product derivatives, particularly their anti-tumor activity. It is worth noting that compared to lead compounds, most natural product derivatives modified with pyrazole exhibit excellent pharmacological activity. Some of these derivatives exhibit outstanding anti-tumor activity, with IC50 values reaching nanomolar levels. This review provides more research directions and choices for future studies on natural products.

Metabolic reprogramming is a hallmark of cancer. Distinct and unusual metabolic aberrations occur during tumor development that lead to the growth and development of tumors. Oncogenic signaling pathways eventually converge to regulate three major metabolic pathways in tumor cells i.e., glucose, lipid, and amino acid metabolism. Therefore, identifying and targeting the metabolic nodes of cancer cells can be a promising intervention and therapeutic strategy for patients with malignancies. The long road of new drug discovery for cancer therapy has necessitated relooking alternative strategies such as drug repurposing. Advanced genomic and proteomic technologies for the assessment of cancer-specific biological pathways have led to the discovery of new drug targets, which provide excellent opportunities for drug repurposing. The development of effective, safe, cheaper, and readily available anticancer agents is the need of the hour, and drug repurposing has the potential to break the current drug shortage bottleneck. This review will accordingly cover various metabolic pathways that are aberrant in cancer, and strategies for targeting metabolic reprogramming by using repurposed drugs.

Sustainable chemistry and nature-friendly protocols are not only luxury but has become essential requirement for the modern society as it progresses towards a more responsible future. To match the current needs of the community, industries and in particular chemical industry is looking for novel and cheap strategies that have less adverse effects on the environment. Heterocyclic compounds are one particular motif, which is prevalent in nature. It is found in a wide range of synthetic and natural compounds, both established and in development as potent therapeutic candidates. According to the US retail market in 2014-2015, heterocyclic moieties constitute the basic skeletons for 80% of marketed pharmaceuticals. However, majority of the synthetic methodologies still uses classical approaches with toxic solvents, stoichiometric reagents, reactions with less atom economy etc. Thus, there is an urgent need for green, sustainable alternatives of the classical reactions. In recent years, an array of diverse approaches and technologies have been discovered by the scientific community to address the issue of eco-friendly manufacture of various pharmaceutically and medicinally important heterocyclic molecules. In this context, the current review will summarize various reported green pathways to the heterocyclic architecture, particularly O, N, and S-heterocyclic compounds. The methods highlighted in this article includes reaction in environment friendly nonconventional media, solvent-free approaches, heterogeneous catalysis, organocatalysis, electrochemical reactions, microwave-mediated reactions, ultrasound-based reactions, enzymatic reactions, biocatalysis, and others.

Topical application of ophthalmic drugs remains to be the preferred delivery method. Eye drops lead the pharmaceutical forms due to ease of application. Despite the poor bioavailability of drugs administered topically, especially related to the dilution and excretion by tear fluid, the absence of controlled drug delivery, and the poor compliance within pediatric and senior populations, eye drops and ointments are still the first choices in eye--related disorders management. Only a few studies have explored the eyelid skin as a site for drug application and transdermal delivery as an alternative route of administration of ophthalmic drugs. Such works have validated the delivery of drugs into the ocular tissues through the eyelid barrier. The eyelid represents a differentiated skin barrier concerning the thickness, the structure of the stratum corneum, the vasculature, and the amount of lipids. This work intends to question why the eyelid, being an accessible, non-invasive, comfortable route of administration is not considered a feasible route for ophthalmic drugs. The eyelid structure is presented, and the anatomical and physiological distinctive characteristics are presented. The work also presents the research work on topical drug application to the eyelid skin that has been published so far.

Currently, the synthesis of bioactive sulfonamides using amino acid as a starting reagent has become an area of research interest in organic chemistry. Over the years, an amine-sulfonyl chloride reaction has been adopted as a common step in traditional sulfonamide synthetic methods. However, recent developments have shown amino acids to be better precursors than amines in the synthesis of sulfonamides. Although amines and amino acids have some structural similarities, using amino acids rather than amines in the synthesis of sulfonamides minimizes several drawbacks. Comparatively, amino acids are preferred to amines as starting reagents in sulfonamide synthesis due to their biological relevance, chirality, stereochemistry, diversity of side chains, orthogonality in functional group manipulation, the potential for peptide and protein synthesis, mild reaction conditions, alignment with green chemistry principles, diverse synthetic applications, easy availability, and economic viability. Amino acids, having the aforementioned properties, offer a versatile platform for the synthesis of sulfonamides with tailored structures. The reaction mechanism of the synthesis of amino acid-derived sulfonamides involves a nucleophilic attack by the amino group on the activated sulfonyl species to produce a sulfonamide functional group. Amino acid-based sulfonamides have numerous pharmacological activities, including antibacterial, antiviral, anticancer, antioxidant, anti-inflammatory, anti-plasmodial, antimalarial, anti-trypanosomal, and insect growth regulatory properties. This review discusses several synthetic processes, emphasizing established ways, cutting- edge techniques, and novel approaches that emphasize the significance of amino acids in the synthesis of sulfonamides. The structure-activity relationship of amino acid-derived sulfonamides and their pharmacological activities are also highlighted.

Organic compounds containing azines, di-imines, or bis-Schiff-bases have two azomethine (-CH=N-) functional groups associated with a bridging component. These constituents have attracted attention from a diversity of disciplines, comprising coordination, medicinal, agriculture chemistry, and organic synthesis, because of their comprehensive chemical reactivity and nature. This study determines common synthetic approaches and various biological and pharmacological activities of several substituted bis-Schiff byproducts. The usefulness of bis-Schiff bases in synthetic chemistry and their potential as inhibitors of a number of enzymes have attracted research attention. We have examined different biological activities and common synthetic methods used to make bis- Schiff bases that have been published in the literature. A systematic search of the literature has been performed, and studies fitting the prearranged inclusion standards have been inspected. This review can open up new potentials for upcoming research in this area and advance our information on bis- Schiff bases.

Hydantoin, a five-membered heterocyclic scaffold, is regarded as a crucial scaffold in medicinal chemistry. Hydantoins have been useful in synthesizing medicines like nilutamide, enzalutamide, and apalutamide. Thiohydantoin and selenohydantoin have been discovered as two separate types of hydantoin. There are two hydrogen bond donors, two hydrogen bond acceptors, and four substitution sites. These characteristics have led to the design, synthesis, and expansion of hydantoin derivatives' biological and pharmacological effects against numerous types of malignancies. This study reviews the recent contributions of hydantoin and its isosteric variants to medicinal chemistry. To emphasize their significance, certain significant compounds based on hydantoins and their structure activity relationships (SAR) are briefly discussed. We thoroughly analyzed each scaffolds' structural characteristics and SAR, and these scaffolds may one day show potential anticancer activities.

The use of biomaterials in treating and managing chronic wounds represents a significant challenge in global healthcare due to the complex nature of these wounds, which are slow to heal and can lead to complications such as frequent infections and diminished quality of life for patients. Chronic wounds, which can arise from conditions like diabetes, poor circulation, and pressure sores, pose distinct challenges in wound care, necessitating the development of specialized dressings. The pathophysiology of chronic wounds is thoroughly examined in this article, with particular attention paid to the cellular and molecular defects at work and the therapeutic guidelines. It also identifies key issues in the field, such as biocompatibility, cost-effectiveness, immune reactions, and regulatory obstacles, while suggesting future research focuses on improving biocompatibility, integrating drug delivery systems, and exploring cellular treatments. Ethical implications, such as patient safety, informed consent, and equitable access to technology, are also discussed. Finally, this review highlights the transformative potential of biomaterials in chronic wound management, urging for continued research and clinical integration to fully harness their capabilities in improving patient care.