Current topics in medicinal chemistry最新文献

Despite ongoing advancements in drug design and developments, breast cancer remains a serious and devastating disease and is ranked as the second most common illness in women. Breast cancer rates have increased significantly during the last 40 years. This necessitates the development of novel treatment techniques. Currently, chemotherapy is the primary mode of treatment for breast cancer; however, its toxicity to normal cells and drug resistance are considered the main obstacles. Researchers are looking for novel anti-breast cancer medication classes to improve cancer therapy efficacy and survival rates. Using non-targeting medicines in a 'one-size-fits-all' strategy can harm healthy cells and may not be effective for all patients. Thus, now, the treatment of breast cancer is exploring targeted-based therapy. The tactics involved in this therapy may improve patient survival rates, but their extended usage can lead to significant side effects and medication resistance. Targeted therapy enables precision medicine by targeting particular oncogenic markers in malignancies. Because of their strong cytotoxicity against several cancer cell types, heterocyclic compounds play an important role in the development of therapeutically effective anticancer drugs. Benzimidazole derivatives have grown in favour of anti-breast cancer medicines in recent years due to their broad biological characteristics and therapeutic applications. This review provides healthcare professionals and researchers with an overview of current breakthroughs (2019-2024) in benzimidazole derivatives as breast cancer-targeted therapy, based on the perspectives of leading experts. We have illuminated the diverse and evolving landscape of hybridized benzimidazole, along with its biological targets and anti-breast cancer activity. Further, we also have compiled the various ongoing clinical trials of benzimidazole scaffolds as anti-breast cancer agents. A detailed illustration of the structure-activity connection with special emphasis is provided. The effort may help to develop potent, selective, and effective drugs to combat breast cancer.

Antibiotics are a revolutionary discovery in modern medicine, enabling the successful treatment of bacterial infections that were once untreatable and deadly. Teixobactin, a "head-toside- chain" cyclodepsipeptide, shows great promise as a lead compound for developing new antibiotics to deal with multi-drug-resistant bacterial infections. The unique pharmacological profile and intriguing structural characteristics of teixobactin, including its unusual amino acid residues (three D-amino acids and L-allo-enduracididine), have drawn the attention of multiple research groups seeking to create new antibiotics with innovative mechanisms. This review explores recent developments in the chemical structure of teixobactin, its biological role in cells, its biosynthetic production pathway, and how it disrupts bacteria (mode of action). Along with the structureactivity relationship (SAR) studies, this review also covers various synthetic approaches used to create teixobactin and its analogs. Finally, some observations regarding emerging patterns during the synthesis of unique analogs of teixobactin, as well as suggestions for further research and developments, are discussed.

Ongoing research and development efforts are currently focused on creating COVID-19 vaccines using a variety of platforms. Among these, mRNA technology stands out as a cuttingedge method for vaccine development. There is a growing public awareness of mRNA and its potential in vaccine development. Despite being relatively recent, extensive scientific research has been dedicated to vaccines for a considerable period. mRNA vaccines are created by synthesizing the spike protein from a DNA template. This review delves into the various aspects of these vaccines and thoroughly explores the intricacies of COVID-19 vaccinations. It is essential to choose a reliable, efficient, and widely accessible vaccine to combat COVID-19. However, due to the possibility of virus mutations, developing a dependable and safe vaccine is crucial to prepare for future outbreaks of SARS-CoV-2 variants. Meanwhile, concerns remain regarding the potential risks associated with these vaccines.

Phenyl amino pyrimidine attracts researchers due to its versatile scaffold and medicinal significance. This significant moiety present in the Imatinib contributed to medicinal chemistry. In this manuscript, we reviewed various derivatives of Imatinib containing 2-phenylaminopyrimidine, which has a variety of roles, especially in the anti-cancer category. This manuscript aims to prepare a scientific report that underscores the novel Imatinib derivatives in the field of chemistry for various activities such as anti-cancer, anti-microbial, and miscellaneous focused on cardiovascular, anti-platelets, and anti-parasitic, etc. Finally, this manuscript may attract researchers for new structure design, and the development of novel phenyl amino pyrimidine scaffolds that are more active and less harmful. We propose a compilation and analysis of around 100 Imatinib derivatives having main chromatophores, such as phenylaminopyrimidine. A large number of researchers are interested in Imatnib-based analogs as they have wide biological potential in the largely developing chemical world of the heterocyclic moiety. The phenylamino pyrimidine moiety became an important moiety for researchers to discover combinational libraries and implement the efforts in search of the lead entities. Phenylaminopyrimidine has been manifesting to be an effective moiety in the current respective disease scenario. It has been discovered that phenylaminopyrimidine and its derivatives have an extensive spectrum of pharmacological potential with numerous applications in academic interest, in the pharmaceutical industry, medicinal chemistry, etc. Imatinib containing phenylaminopyrimidine and its novel synthetic derivatives are a prominent heterocyclic compound class with intriguing use in medicinal chemistry. Thus, in brief, attention should be given to other chemical approaches for synthesizing novel compounds containing phenylaminopyrimidine moiety, hence potentiating their efficacy.

Transient receptor potential vanilloid (TRPV) channels are a member of the TRP superfamily, which consists of six proteins and is expressed in many neuronal and non-neuronal cells. Among them, TRPV1-4 are non-selective cation channels that are highly sensitive to temperature changes, while TRPV5-6 are channels that are highly selective to Ca2+. These cation channels have attracted great interest academically, especially from a pharmacological perspective. TRPV channels play a vital role in many physiological processes and can be regulated by a variety of endogenous stimuli as well as a range of natural and synthetic compounds. The regulation of their activities can lead to a variety of diseases and disorders, such as neurodegenerative diseases, pain, cancer, and skin diseases. In fact, several TRPV1 and TRPV3 modulators have been developed for clinical use. Therefore, the development of TRPV channel modulators has important clinical significance and value. Herein, we focused on and summarized the latest research progress of endogenous and exogenous ligands of six TRPV channels and their pharmacological effects on related diseases.

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.