Current topics in medicinal chemistry最新文献

Background: Piperidines are among the essential synthetic fragments for designing drugs and play a significant role in the pharmaceutical industry. The synthesis of newer derivatives by incorporating different amines paves the way for the introduction of novel drug combinations for current cancer treatments.

Method: The new combinations of 1-(4-bromo-2-(pyrrolidine-1-yl) benzyl) piperidine derivatives were synthesized by adding various amino groups. All the synthesized derivatives were characterized using NMR and LC-MS. The anti-cancer activity of all the synthesized derivatives was studied on three different cell lines, A549 (lung cancer), HCT-116 (colon cancer), and MCF-7(breast cancer), using an MTT assay. The most potent compounds, 7h and 7k were further evaluated for cell cycle and tubulin polymerization inhibitory activity. Further, in-silico analysis for the same properties was performed using molecular docking using MM/GBSA and validated by RMSD.

Results: All the synthesized derivatives showed selective cytotoxic potential against different cancer cell lines. Most of the derivatives displayed comparable anticancer potential in comparison to 5-FU. The most potent derivative, 7h, further arrests the cancer cells in the G2/M phase and prevents tubulin polymerization. The same was further confirmed using molecular docking on the colchicine binding site.

Conclusion: The derivative that arrests the cancer cells in the G2/M phase of the cell cycle and induces depolymerization can be developed as a good lead for further development.

Background: Scedosporium apiospermum is a multidrug-resistant filamentous fungus that causes localized and disseminated diseases. Our group has previously described that metalbased complexes containing copper(II) or silver(I) ions complexed with 1,10-phenanthroline-5,6- dione (phendione) inhibited the viability of S. apiospermum conidial cells.

Objective: The effects of these promising complexes, [Cu(phendione)3](ClO4)2.4H2O (Cuphendione) and [Ag(phendione)2]ClO4 (Ag-phendione), on vital biological processes, production of key virulence attributes and interaction events of S. apiospermum were investigated using a comprehensive multimodal approach.

Results: The results demonstrated that both Cu-phendione and Ag-phendione effectively inhibited the viability of S. apiospermum mycelial cells in a dose-dependent manner. Furthermore, these test complexes, at varying concentrations, inhibited the transition of S. apiospermum conidia into hyphae. Scanning electron microscopy revealed significant structural alterations in the fungal cells, including changes to surface sculpturing and overall morphological architecture, following treatment with the complexes. A marked reduction in the expression of key surface molecules, such as mannose/glucose-rich glycoconjugates, fibronectin-binding proteins, and the well-known adhesin peptidorhamnomannan further supported these ultrastructural changes. The treatment also impaired adhesive interactions, reducing the fungus's ability to form biofilms on polystyrene surfaces and diminishing its interaction with macrophages, lung epithelial cells, and fibroblasts. Notably, treatment of infected macrophages with the complexes led to a significant reduction in the number of intracellular fungal cells.

Conclusion: The results provide information about the effects of silver- and copper-phendione complexes on cellular and virulence aspects of the emerging fungus S. apiospermum.

Flavonoids belong to the polyphenol group that naturally exists in fruits, vegetables, tea, and grains. Flavonoids, as secondary metabolites, show indispensable contributions to biological processes and the responses of plants to numerous environmental factors. The bioactivity of flavonoids depends on C6-C3-C6 ring substitution patterns that exhibit bioactive antioxidant, antimicrobial, antifungal, antitumor, and anti-inflammatory properties. The synthesis of flavonoids has been reported by various methodologies. Therefore, the present review systematically summarizes the synthesis of recent heterocyclic flavonoid derivatives via facile synthetic approaches since the research in flavonoids is useful for therapeutic and biotechnology fields.

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.