Natural Product Reports, Год журнала: 2023, Номер 40(10), С. 1595 - 1607
Опубликована: Янв. 1, 2023
Limited screening focus has led to most marine derived indole alkaloids (MIA) being inactive. However, computational comparisons with drugs suggest MIAs will be active in new disease relevant targets if a shift is adopted.
Язык: Английский
Phytomedicine, Год журнала: 2024, Номер 134, С. 155972 - 155972
Опубликована: Авг. 30, 2024
Язык: Английский
Процитировано
16
ACS Nano, Год журнала: 2024, Номер unknown
Опубликована: Сен. 27, 2024
Radiation therapy, a fundamental treatment for tumors, is often accompanied by radiation-induced skin injury (RISI). Excessive production of reactive oxygen species (ROS) and subsequent inflammation are two key factors in RISI development that will cause affect radiotherapy. Herein, the co-assembled binary polyphenol natural products inspired dual-functional cascade microneedle system prevention RISI. Specifically, epigallocatechin gallate (EGCG) curcumin (CUR) were into nanoparticles (CEPG) intermolecular interactions then incorporated with catalase (CAT) to achieve microneedles (this was conducive penetrate epidermal keratinocytes where had greatest impact). When using microneedles, tip dissolved rapidly delivered CEPG CAT dermis, NPs able respond ROS decompose EGCG CUR. More importantly, formed converts superoxide anions water step-by-step, which can reduce cell damage caused free radicals early stages radiation prevention; meanwhile, CUR inhibited inflammatory pathways, achieving post-radiotherapy period. These explorations broaden strategy application
Язык: Английский
Процитировано
11
Frontiers in Pharmacology, Год журнала: 2025, Номер 15
Опубликована: Янв. 7, 2025
Mitochondria, as the energy factories of cells, are involved in a wide range vital activities, including cell differentiation, signal transduction, cycle, and apoptosis, while also regulating growth. However, current pharmacological treatments for stroke challenged by issues such drug resistance side effects, necessitating exploration new therapeutic strategies. This review aims to summarize regulatory effects natural compounds targeting mitochondria on neuronal mitochondrial function metabolism, providing perspectives treatment. Numerous vitro vivo studies have shown that products berberine, ginsenosides, baicalein protect reduce stroke-induced damage through multiple mechanisms. These apoptosis modulating expression mitochondrial-associated apoptotic proteins. They inhibit activation permeability transition pore (mPTP), thereby decreasing ROS production cytochrome C release, which helps preserve function. Additionally, they regulate ferroptosis, fission, promote autophagy trafficking, further enhancing protection. As multi-target chemical agents, offer high efficacy with fewer present promising potential innovative therapies. Future research should investigate effectiveness safety these clinical applications, advancing their development strategy stroke.
Язык: Английский
Процитировано
2
Journal of Medicinal Chemistry, Год журнала: 2023, Номер 66(4), С. 2946 - 2963
Опубликована: Фев. 14, 2023
Natural products provide inspiration and have proven to be the most valuable source for drug discovery. Herein, we report a scaffold hybrid strategy of Tanshinone I discovery NLRP3 inflammasome inhibitors. 36 compounds were designed synthesized, cheminformatic analyses showed that these occupy unique chemical space. The biological evaluation identified 5j, 12a, 12d as inhibitors with significant potency, selectivity, drug-likeness. Mechanistic studies revealed derivatives could inhibit degradation protein block oligomerization NLRP3-induced apoptosis-associated speck-like proteins, thus inhibiting activation. In addition, water solubility, in vitro metabolic stability, oral bioavailability also greatly improved compared I. Therefore, this protocol provides new structural evolution class potent
Язык: Английский
Процитировано
22
Phytochemistry Reviews, Год журнала: 2024, Номер unknown
Опубликована: Март 28, 2024
Язык: Английский
Процитировано
9
Nature Chemical Biology, Год журнала: 2024, Номер unknown
Опубликована: Июнь 21, 2024
Metabolic alterations in cancer precipitate associated dependencies that can be therapeutically exploited. To meet this goal, natural product-inspired small molecules provide a resource of invaluable chemotypes. Here, we identify orpinolide, synthetic withanolide analog with pronounced antileukemic properties, via orthogonal chemical screening. Through multiomics profiling and genome-scale CRISPR-Cas9 screens, orpinolide disrupts Golgi homeostasis mechanism requires active phosphatidylinositol 4-phosphate signaling at the endoplasmic reticulum-Golgi membrane interface. Thermal proteome genetic validation studies reveal oxysterol-binding protein OSBP as direct phenotypically relevant target orpinolide. Collectively, these data reaffirm sterol transport actionable dependency leukemia motivate ensuing translational investigation probe-like compound
Язык: Английский
Процитировано
9
Pharmacology & Therapeutics, Год журнала: 2024, Номер 264, С. 108752 - 108752
Опубликована: Ноя. 16, 2024
Язык: Английский
Процитировано
9
European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 282, С. 117088 - 117088
Опубликована: Ноя. 22, 2024
Язык: Английский
Процитировано
9
Journal of Photochemistry and Photobiology C Photochemistry Reviews, Год журнала: 2024, Номер 58, С. 100653 - 100653
Опубликована: Янв. 25, 2024
Язык: Английский
Процитировано
8
Nature Chemistry, Год журнала: 2024, Номер 16(6), С. 945 - 958
Опубликована: Фев. 16, 2024
Abstract The efficient exploration of biologically relevant chemical space is essential for the discovery bioactive compounds. A molecular design principle that possesses both biological relevance and structural diversity may more efficiently lead to compound collections are enriched in diverse bioactivities. Here pseudo-natural product (PNP) strategy, which combines PNP concept with synthetic diversification strategies from diversity-oriented synthesis, reported. collection was synthesized a common divergent intermediate through developed indole dearomatization methodologies afford three-dimensional frameworks could be further diversified via intramolecular coupling and/or carbon monoxide insertion. In total, 154 PNPs were representing eight different classes. Cheminformatic analyses showed structurally between Biological investigations revealed extent bioactivity enrichment four inhibitors Hedgehog signalling, DNA de novo pyrimidine biosynthesis tubulin polymerization identified
Язык: Английский
Процитировано
8