Current topics in medicinal chemistry最新文献

Visible-light-mediated reactions have recently emerged as a powerful strategy for the synthesis of diverse organic molecules under mild reaction conditions. Usually, the reactions are performed at room temperature and thus sensitive functional groups remain unaffected. Thus, this protocol has received intense interest from academia as well as industries. The heterocycles, in general, are of much interest because of their biological activities and application in therapeutics. The Oxygen- and Sulfur-containing heterocyclic compounds have recently attracted attention as these compounds showed promising activities as anti-cancer drugs, antibiotics, antifungal and anti-inflammatory agents among other applications. The synthesis of this class of compounds by efficient and greener routes has become an important target. This review highlights the various procedures for the synthesis of these compounds and their derivatives under visible light-induced reactions. The green aspects and mechanism of each procedure have been discussed.

Isatin or 1H-indole-2,3-dione skeleton has been playing a significant role in drug design and development. Isatin itself and many of its derivatives are widely distributed in naturally occurring bioactive compounds. Various synthetic isatin derivatives were found to possess a broad range of significant pharmacological efficacies especially anti-cancer activity against a wide variety of cancer cell lines. Interestingly, on a few occasions, some isatin-derived scaffolds were reported as more potent than the tested reputed drug molecules. As a result, isatin-derived compounds have been gaining significant attention in cancer-based drug developments. In this review, we have summarized literature reported during the last two decades related to the synthesis of structurally diverse isatin-derived scaffolds with promising anti-cancer activities.

Osteoarthritis (OA) is a common chronic articular degenerative disease characterized by articular cartilage degradation, synovial inflammation/immunity, and subchondral bone lesions. Recently, increasing interest has been devoted to treating or preventing OA with herbal medicines. The mechanism of action of plant raw materials used in osteoarthrosis treatment is well documented. They are sought after because of the high frequency of inflammation of the knee joint among both elderly and young people engaged in sports in which their knee joints are often exposed to high-stress conditions. The purpose of this work was to present some most effective and safe plant medicines with proven mechanisms of action that can help to alleviate the growing social problem of osteoarthrosis caused in recent years. A review of the available literature based primarily on the latest editions of ESCOP and EMA monographs and the latest scientific papers has made it possible to select and propose medical management of osteoarthrosis by ranking plant medicines according to their effectiveness. Clinical studies of raw plant materials, such as Harpagophyti radix, Olibanum indicum, and Urticae foliumet herba have indicated that these drugs should be considered the first choice in osteoarthrosis treatment. The efficacy of Rosae pseudo-fructus, Salicis cortex, Filipendulae ulmariae flos et herba, Ribis nigri folium, and externally applied Capsici fructus and Symphyti radix, has also been proven by pharmacological studies. All the plant medicines mentioned in the paper have been studied in detail in terms of their phytochemistry, which can help doctors in their decisionmaking in the treatment of osteoarthrosis.

N-heterocycles represent a predominant and unique class of organic chemistry. They have received a lot of attention due to their important chemical, biomedical, and industrial uses. Food and Drug Administration (FDA) approved about 75% of drugs containing N-based heterocycles, which are currently available in the market. N-Heterocyclic compounds exist as the backbone of numerous natural products and act as crucial intermediates for the construction of pharmaceuticals, veterinary items, and agrochemicals frequently. Among N-based heterocyclic compounds, bioactive N,N-heterocycles constitute a broad spectrum of applications in modern drug discovery and development processes. Cefozopran (antibiotic), omeprazole (antiulcer), enviradine (antiviral), liarozole (anticancer), etc., are important drugs containing N,N-heterocycles. The synthesis of N,N-heterocyclic compounds under sustainable conditions is one of the most active fields because of their significant physiological and biological properties as well as synthetic utility. Current research is demanding the development of greener, cheaper, and milder protocols for the synthesis of N,N-heterocyclic compounds to save mother nature by avoiding toxic metal catalysts, extensive application of energy, and the excessive use of hazardous materials. Nanocatalysts play a profound role in sustainable synthesis because of their larger surface area, tiny size, and minimum energy; they are eco-friendly and safe, and they provide higher yields with selectivity in comparison to conventional catalysts. It is increasingly demanding research to design and synthesize novel bioactive compounds that may help to combat cancer since the major causes of death worldwide are due to cancer. Hence, the important uses of nanocatalysts for the one-pot synthesis of biologically potent N,N-heterocycles with anticancer activities have been presented in this review.

Hydroxamic acids (HAs) are chemical compounds characterized by the general structure RCONR'OH, where R and R' can denote hydrogen, aryl, or alkyl groups. Recognized for their exceptional chelating capabilities, HAs can form mono or bidentate complexes through oxygen and nitrogen atoms, rendering them remarkably versatile. These distinctive structural attributes have paved the way for a broad spectrum of medicinal applications for HAs, among which their pivotal role as inhibitors of essential Ni(II) and Zn(II)-containing metalloenzymes. In 1962, a significant breakthrough occurred when Kobashi and colleagues identified hydroxamic acids (HAs) as potent urease inhibitors. Subsequent research has increasingly underscored their capability in combatting infections induced by ureolytic microorganisms, including Helicobacter pylori and Proteus mirabilis. However, comprehensive reviews exploring their potential applications in treating infections caused by ureolytic microorganisms remain scarce in the scientific literature. Thus, this minireview aims to bridge this gap by offering a systematic exploration of the subject. Furthermore, it seeks to explore the significant advancements in obtaining hydroxamic acid derivatives through environmentally sustainable methodologies.

This review highlights major developments in the application of green organocatalytic and enzymatic dynamic kinetic resolutions (DKRs) in the total synthesis of biorelevant scaffolds. It illustrates the diversity of useful bioactive products and intermediates that can be synthesized under greener and more economic conditions through the combination of the powerful concept of DKR, which allows the resolution of racemic compounds with up to 100% yield, with either asymmetric organocatalysis or enzymatic catalysis, avoiding the use of toxic and expensive metals. With the need for more ecologic synthetic technologies, this field will undoubtedly expand its scope in the future with the employment of other organocatalysts/enzymes to even more types of transformations, thus allowing powerful greener and more economic strategies to reach other biologically important molecules.

Alzheimer's Disease (AD), a prevalent neurodegenerative disorder, poses a significant global health challenge with complicated pathogenesis. Pathological characteristics of AD include increasing loss of cholinergic neurons, oxidative stress, mitochondrial dysfunction, and amyloid beta accumulation. Due to the limited availability of effective therapeutic options with only symptomatic relief and their severe adverse effects, there is a significant need to search and explore new agents for the management of AD. Recently, natural products and/or phytoconstituents of plants have gained notable attention as potential sources of neuroprotective agents due to their diverse chemical constituents, mechanism of action, and relatively safe profiles. In view of this, Glycyrrhiza glabra has been recognized for its several therapeutic properties in traditional medicine systems for centuries. Further, neuroactive phytoconstituents of this plant, including glycyrrhizin, liquiritigenin, isoliquiritigenin, glabridin, and glycyrrhizic acid, exhibit significant pharmacological advantages along with potential neuroprotective effects against AD. Glycyrrhiza glabra and its phytoconstituents have gained significant interest due to its ability to exert a neuroprotective impact by influencing multiple signaling pathways, inhibiting AChE and BACE1 activity, reducing Aβ accumulation, plaque formation, and tau phosphorylation, and quenching the free radical in experimentally-induced AD-like brain. The present review summarizes available in vitro and in vivo preclinical studies that have been performed to evaluate the beneficial neuroprotective effect of Glycyrrhiza glabra and its phytoconstituents against AD-like pathology. Based on available facts, it can be concluded that neuroactive phytoconstituents of Glycyrrhiza glabra could be significant lead molecules for the drug discovery of anti-AD medicines in the future.

Introduction/objective: Tuberculosis (TB) remains a persistent global health challenge, with an increasing incidence of cases and limitations in current treatment strategies. Traditional therapy involves long drug treatments that can cause side effects and lead to drug-resistant strains, making treatment less effective. This study aimed to explore the therapeutic potential of a novel nanoparticle-based delivery system for Thymol (THY), a natural antibacterial bioactive molecule, to combat Mycobacterium smegmatis, a model organism for Mycobacterium tuberculosis.

Methods: A nanoparticle-based delivery system was developed using biocompatible Thymolconjugated Chitosan Zinc Ferrite Nanoparticles (THY-CH-ZnFe2O4 NPs). The nanoconjugates were characterized for their morphological and chemical properties.

Results: The characterization of synthesised nanoparticles showed THY-CH-ZnFe2O4 NPs to exhibit enhanced biocompatibility and antibacterial activity against M. smegmatis compared to THY alone. The nanoconjugates induced Reactive Oxygen Species (ROS)-mediated damage to the bacterial cell membrane, effectively inhibiting bacterial replication, dormancy, and biofilm formation. Additionally, the nanoconjugates demonstrated low cytotoxicity towards the human kidney cell line.

Conclusion: The study's findings highlighted a new direction for developing nanoparticle-based antimycobacterial agents with a wide application in treating TB and other bacterial diseases. The THY-CH-ZnFe2O4 NPs show promise as a safe and effective therapeutic agent, offering a potential solution to the limitations of current TB treatment strategies.

Despite extensive research, there is an unmet need for developing disease-modifying therapies for Parkinson's disease (PD). Failure of certain landmark clinical trials has highlighted the need for a better understanding of the disease pathogenesis as well as identifying the hurdles in developing drug candidates and designing clinical trials. While adhering to these needs, several promising trials are currently underway with the hope of developing reliable targets. There is also a need to conduct research on plant-based natural products and use them as therapeutic candidates for PD. In this context, many studies have demonstrated the efficacy of medicinal plants and their principal phytochemicals. This review provides an update on the presently underway clinical trials with a small emphasis on the disease modifying therapies that target small molecules, mitochondria, and oligodendrocytes. The role of ethnopharmacology-based approaches for treatment of PD has also been discussed. The third aspect of the article considers the importance of nanomedicine in this area, including the use of liposomes and nanoparticles to provide a novel approach for the treatment of PD.

Introduction: DNA repeats and motifs are specific nucleotide patterns/DNA sequences frequently present in the genomes of prokaryotes and eukaryotes. Computational identification of these discrete patterns is of considerable importance since they are associated with gene regulation, genomic instability, and genetic diversity and result in a variety of diseases/disorders.

Objective: In this article, the myriad of computational tools/algorithms and databases (~200 distinct resources) implicated in the detection of DNA repeats and motifs have been enlisted. This article will not only provide guidance to the users regarding the accuracy, reliability, and popularity (reflected by the citation index) of currently available tools but also enable them to select the best tool(s) to carry out a desired task.

Methods: The structured literature review, with its dependable and reproducible research process, allowed us to acquire 200 peer-reviewed publications from indexing databases, such as Scopus, ScienceDirect, Web of Science (WoS), PubMed, and EMBASE, by utilizing PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) regulations. Numerous keyword combinations regarding DNA repeats and motifs were used to create the query syntax.

Results: Initially, 3,233 research publications were retrieved, and 200 of them that satisfied the eligibility criteria for the detection and identification of DNA repeats and motifs by computational tools were chosen. A total of 200 research publications were recovered, of which 99 dealt with repeat prediction tools, 12 with repetitive sequence databases, 19 with specialized regulatory element databases, and 69 with motif prediction tools.

Conclusion: This article lists numerous databases and computational tools/algorithms (~ 200 different resources) that are involved in the identification of DNA repeats and motifs. It will help users choose the appropriate tool(s) for carrying out a particular task in addition to offering guidance on the reliability, dependability, and popularity (as indicated by the citation index) of currently available tools.