Mini reviews in medicinal chemistry最新文献

Introduction: Dendrobium belongs to one of the most important genera of the Orchidaceae family, which covers the largest category of flowering plants. More recent traditional medicinal studies have revealed that these orchid plants are used worldwide to treat a variety of illnesses, including those related to the complexion, pulmonary, gastrointestinal, reproductive, and circulatory systems, as well as cancers, pain, and inflammation. Several Dendrobium species have been the subject of phytochemistry and pharmacological research to explore their different medicinal aspects.

Materials and methods: A comprehensive search through databases (PubMed, Google Scholar, Web of Science, Traditional integrated knowledge resources, local dissertations, and books) was conducted up until November 2024 using key terms such as "Orchid plants, Type 2 diabetes, phytomedicine, natural products, phytoconstituents, phytochemistry, therapeutic potential, and plantderived antidiabetic agents."

Results: Its major phytoconstituents belong to the chemical categories of stilbenoid, glycoside, alkaloids, flavonoids, phenanthrenes, anthocyanins, carotenoids, and bibenzyl derivatives, in which the alkaloids and flavonoids play a most significant role for their biological properties. The flavone Cglycoside and flavanols are commonly found, but highly methylated and glycosylated derivatives of flavonoids are absent in orchid leaves.

Discussion: The phytochemical composition of Dendrobium, along with its structure-activity relationship of major classes, supports it as a potential source for novel antidiabetic agents through integrating traditional knowledge with medicinal chemistry aspects.

Conclusion: A specific Dendrobium orchid plant has a promising role in the effective management of diabetes. In the future, newer, more potent antidiabetic compounds may be isolated and further developed into more effective antidiabetic agents.

Glucose control remains the primary target in the treatment of both Type 1 and Type 2 diabetes. Glycemia plays a major role in preventing both macrovascular and microvascular complications. Some diabetes medications can also affect body weight. This article describes the various categories of antidiabetic medications and their effects on weight and HbA1c (Hemoglobin A1c) levels in patients with Type 1 and Type 2 diabetes. The weight and glycemic control effects of antidiabetic drugs approved for the management of weight loss are also reviewed in this article. Several types of medications are available that work through different mechanisms to help lower blood glucose levels. The risk of weight gain or weight loss depends on both the medication used and lifestyle factors such as diet and exercise. A reduction in glycosuria is the primary reason for weight gain; however, reducing calorie intake can help minimize this effect. Nevertheless, due to limited access to adequate nutrition education, many people are unable to complement changes in medical therapy with necessary lifestyle adjustments. Some diabetes medications can cause weight loss by getting rid of extra glucose from the body or lowering the amount of glucose our liver makes. Some diabetes medications have little to no effect on weight for most people, and healthcare professionals sometimes refer to these as "weight-neutral" diabetes medications. Certain medications promote weight loss in addition to exerting extra-glycemic and extra-pancreatic effects, which positively impact cardiovascular risk by reducing both mortality and morbidity. Verification and further explanation of the actual mechanisms underlying the life-prolonging effects of these antidiabetic medications are still needed. Their effects on biomarkers that mimic calorie restriction in patients also require confirmation. Additional research should be conducted to clarify the details of lifespan extension. Furthermore, when herbs are administered alongside antidiabetic medicines, they may alter the pharmacokinetic and pharmacodynamic properties of the drugs, rendering them less effective or potentiating their activity and producing adverse effects.

Imidazo[2,1-b][1,3,4]thiadiazoles, a class of fused bicyclic heterocycles, have garnered significant interest in medicinal chemistry due to their diverse biological activities, particularly their anticancer properties. Over recent decades, extensive research has been conducted to explore and enhance their therapeutic potential. This comprehensive review spans six decades of research on the imidazo[2,1-b][1,3,4]thiadiazole scaffold, focusing on structural variations at C-2, C-5, and C-6 position on this scaffold and their implications for anticancer activity. Modifications at these positions have been shown to significantly impact the compound's efficacy against various cancer cell lines. Continuous exploration and optimization of these substitutions hold promise for the development of novel anticancer therapeutics.

As the main fermentation product of Aspergillus fumigatus (A. fumigatus), fumagillin is directly related to the gene of A. fumigatus and exhibits a variety of biological activities. However, its clinical application is limited by low yield and toxicity. It is of great significance to improve the yield and safety of fumagillin using A. fumigatus. Currently, research on fumagillin at home and abroad primarily focuses on a single direction and lacks a systematic review of its biosynthesis, structure-activity relationship, and strain modification technology, as well as a comprehensive theoretical framework. This study systematically reviews the biosynthesis mechanism, activity characteristics, and targeted strain modification technology of fumagillin, providing theoretical support for breakthroughs in production, toxicity regulation, and clinical transformation of fumagillin.

Malaria has been one of the most lethal infectious diseases throughout history, claiming a high number of human lives. The genomic plasticity of Plasmodium falciparum, the causative agent of the most severe and deadly form of malaria, gives the parasite a constant resistance to drugs developed for its control. Despite efforts to control and even eradicate the disease, these have largely been unsuccessful due to the parasite's continuous adaptations. This study aims to examine the key genes involved in parasite resistance and propose a shift in the combat strategy. Gene silencing techniques offer promise in combating malaria, yet further research is needed to harness their potential for disease control fully. Although there is still a long way to go for the implementation of gene silencing-based therapeutic strategies, this review addresses examples of the use of such techniques in various human diseases and how they could be extrapolated for malaria 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 mini-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).

While the use of plants in traditional medicine dates back to 1500 B.C., modern advancements led to the development of innovative therapeutic techniques. On the other hand, in the field of anti-infective agents, lack of efficacy and the onset of resistance stimulate the search for novel agents. Genus Artemisia is one of the most diverse among perennial plants with a variety of species, properties, and chemical components. The genus is known for its therapeutic values and, in particular, for its role in the origin of antimalarial agents derived from artemisinin. In this review, we aim to provide an updated overview of the evolution of natural and nature-inspired compounds related to the genus Artemisia that have been proven, in vitro and in vivo, to possess antimalarial properties. An overview of the chemical composition and a description of the ethnopharmacological aspects will be presented, as well as an updated report on in vitro and in vivo evidence that allowed the translation of artemisinin and its derivatives from traditional chemistry into modern medicinal chemistry. The biological and structural properties will be discussed, also dedicating attention to the challenging tasks that still are open, such as the identification of optimal combination strategies, the routes of administration, and the full assessment of the mechanism of action.

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.

Quinoxaline molecule has gathered great attention in medicinal chemistry due to its vide spectrum of biological activities and has emerged as a versatile pharmacophore in drug discovery and development. Its structure comprises a bicyclic ring of benzopyrazine and displays a range of pharmacological properties, including antibacterial, antifungal, antiviral, anticancer, and antiinflammatory. This study aims to summarize the different strategies for the synthesis of quinoxalines and their anti-inflammatory properties acting through different mechanisms. Structure-activity relationships have also been discussed in order to determine the effect of structural modifications on anti-inflammatory potential. These analyses illuminate critical structural features required for optimal activity, driving the design and synthesis of new quinoxaline analogues with better antiinflammatory activities. The anti-inflammatory properties of quinoxalines are attributed to their inhibitory action on the expression of several inflammatory modulators such as cyclooxygenase, cytokines, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and p38α Mitogen Activated Protein Kinase (p38α MAPK). Activators of nuclear factor erythroid 2-related factor 2 (NRF2) and agonistic effect on opioid receptors have also been discussed. Hence, this study may provide a future template for the design and development of novel quinoxaline derivatives acting through different molecular targets as potential anti-inflammatory agents with better efficacy and safety profiles.

The broad-spectrum action and capacity to target drug-resistant infections make synthetic Antimicrobial Peptides (AMPs) popular therapeutic agents. Indeed, the effective use of these peptides in clinical application relies on a thorough understanding of their Pharmacokinetic (PK) and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) characteristics. Despite growing research on synthetic AMPs, there is a notable gap in the literature specifically addressing their ADMET profiles. Previous reviews have not extensively covered this area, providing a vital opportunity to study synthetic AMPs' pharmacokinetics and safety, which are crucial for their therapeutic development. This review covered research studies that focused on PK and ADMET of synthetic antimicrobial peptides from several databases, including Google Scholar, SCOPUS, PubMed, and Science Direct, within the years 2020 to 2024, and 12 related research papers have been found. AMPs display a wide range of PK behaviors, including rapid renal clearance, liver-centric distribution, broad distribution with low toxicity, high kidney retention, and gradual absorption with dose-dependent toxicity. Overall, the ADMET profiles of AMPs are crucial in assessing their therapeutic potential, and continuous study is necessary to enhance their practical feasibility. An in-depth investigation of the in vivo ADMET and pharmacokinetic profiles of synthetic AMPs is presented in this review to address the current gap in the research. The findings of this study provide important insights for developing synthetic AMPs as effective antimicrobial drugs.