"AquaF" Building Blocks for Water-Compatible SN2 18F-Fluorination of Small-Molecule Radiotracers.

Despite the widespread use of hydrophilic building blocks to incorporate 18F and improve tracer pharmacokinetics, achieving effective leaving group-mediated nucleophilic 18F-fluorination in water (excluding 18F/19F-exchange) remains a formidable challenge. Here, we present a water-compatible SN2 leaving group-mediated 18F-fluorination method employing preconjugated "AquaF" (phosphonamidic fluorides) building blocks. Among 19 compact tetracoordinated pentavalent P(V)-F candidates, the "AquaF" building blocks exhibit superior water solubility, sufficient capacity for 18F-fluorination in water, and excellent in vivo metabolic properties. Two nitropyridinol leaving groups, identified from a pool of leaving group candidates that further enhance the precursor water solubility, enable 18F-fluorination in water with a 10-2 M-1 s-1 level reaction rate constant (surpassing the 18F/19F-exchange) at room temperature. With the exergonic concerted SN2 18F-fluorination mechanism confirmed, this 18F-fluorination method achieves ∼90% radiochemical conversions and reaches a molar activity of 175 ± 40 GBq/µmol (using 12.2 GBq initial activity) in saline for 12 "AquaF"-modified proof-of-concept functional substrates and small-molecule 18F-tracers. [18F]AquaF-Flurpiridaz demonstrates significantly improved radiochemical yield and molar activity compared to 18F-Flurpiridaz, alongside enhanced cardiac uptake and heart/liver ratio in targeted myocardial perfusion imaging, providing a comprehensive illustration of "AquaF" building blocks-assisted water-compatible SN2 18F-fluorination of small-molecule radiotracers.

18F-Labeled dihydropyridines via Hantzsch reaction for positron emission tomography of P-glycoprotein dysfunction.

Despite the availability of various 11C-labeled positron emission tomography (PET) tracers for assessing P-glycoprotein (P-gp) function, there are still limitations related to complex metabolism, high lipophilicity, and low baseline uptake. This study aimed to address these issues by exploring a series of customized dihydropyridines (DHPs) with enhanced stability and reduced lipophilicity as alternative PET tracers for P-gp dysfunction. Compared with verapamil and the rest DHPs, dimethyl 4-(4-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (1) exhibited superior cellular uptake differences between the human gastric cancer cell line SGC7901 and its drug-resistant counterpart. [18F]1 is successfully synthesized using a novel "hot-Hantzsch" approach in 22.1 ± 0.1 % radiochemical yields. MicroPET/CT imaging demonstrated that the uptake of [18F]1 in the brains of P-gp blocked mice increased by > 3 times compared to the control group. Additionally, [18F]1 displayed favorable lipophilicity (log D = 2.3) and excellent clearance characteristics, making it a promising tracer candidate with low background noise and high contrast.

Bioactive polysaccharides from Momordica charantia as functional ingredients: a review of their extraction, bioactivities, structural-activity relationships, and application prospects.

Momordica charantia L. is a well-known medicine and food homology plant with high pharmaceutical and nutritional values. Polysaccharides are carbohydrate polymers connected by glycosidic bonds, one of the key functional ingredients of M. charantia. Recently, M. charantia polysaccharides (MCPs) have attracted much attention from industries and researchers due to their anti-oxidant, anti-tumor, anti-diabetes, anti-bacteria, immunomodulatory, neuroprotection, and organ protection activities. However, the development and utilization of MCPs-based functional foods and medicines were hindered by the lack of a deeper understanding of the structure-activity relationship (SAR), structural modification, applications, and safety of MCPs. Herein, we provide an overview of the extraction, purification, structural characterization, bioactivities, and mechanisms of MCPs. Besides, SAR, toxicities, application, and influences of the modification associated with bioactivities are spotlighted, and the potential development and future study direction are scrutinized. This review provides knowledge and research underpinnings for the further research and application of MCPs as therapeutic agents and functional food additives.

Extraction, purification, characteristics, bioactivities, prospects, and toxicity of Lilium spp. polysaccharides.

The genus Lilium has been widely used worldwide as a food and medicinal ingredient in East Asia for over 2000 years due to its higher nutritional and medicinal value. Polysaccharide is the most important bioactive ingredient in Lilium spp. and has various health benefits. Recently, Lilium spp. polysaccharides (LSPs) have attracted significant attention from industries and researchers due to their various biological properties, such as antioxidant, immunomodulatory, antitumor, antibacterial, hypoglycaemic, and anti-radiation. However, the development and utilization of LSP-based functional biomaterials and medicines are limited by a lack of comprehensive understanding regarding the structure-activity relationships (SARs), industrial applications, and safety of LSPs. This review provides an inclusive overview of the extraction, purification, structural features, bioactivities, and mechanisms of LSPs. SARs, applications, toxicities, and influences of structural modifications on bioactivities are also highlighted, and the potential development and future study direction are scrutinized. This article aims to offer a complete understanding of LSPs and provide a foundation for further research and application of LSPs as therapeutic agents and multifunctional biomaterials.

Comparatively analyzing of chloroplast genome and new insights into phylogenetic relationships regarding the genus Stephania.

The medicinal plant of the genus Stephania holds significant economic importance in the pharmaceutical industry. However, accurately classifying and subdividing this genus remains a challenge. Herein, the chloroplast (cp) genomes of Stephania and Cyclea were sequenced, and the primary characteristics, repeat sequences, inverted repeats regions, simple sequence repeats, and codon usage bias of 17 species were comparatively analyzed. Twelve markers were identified through genome alignment and sliding window analysis. Moreover, a molecular clock analysis revealed the divergence between subgenus (subg.) Botryodiscia and the combined Cyclea, subg. Stephania and Tuberiphania during the early Oligocene epoch. Notably, the raceme-type inflorescence represents the ancestral state of the Stephania and Cyclea. The genetic relationships inferred from the cp genome and protein-coding genes exhibited similar topologies. Additionally, the paraphyletic relationship between the genera Cyclea and Stephania was confirmed. Bayesian inference, maximum likelihood, and neighbor-joining trees consistently showed that section Tuberiphania and Transcostula were non-monophyletic. In conclusion, this research provides valuable insights for further investigations into species identification, evolution, and phylogenetics within the Stephania genus.

Bioactive polysaccharides from lotus as potent food supplements: a review of their preparation, structures, biological features and application prospects.

Lotus is a famous plant of the food and medicine continuum for millennia, which possesses unique nutritional and medicinal values. Polysaccharides are the main bioactive component of lotus and have been widely used as health nutritional supplements and therapeutic agents. However, the industrial production and application of lotus polysaccharides (LPs) are hindered by the lack of a deeper understanding of the structure-activity relationship (SAR), structural modification, applications, and safety of LPs. This review comprehensively comments on the extraction and purification methods and structural characteristics of LPs. The SARs, bioactivities, and mechanisms involved are further evaluated. The potential application and safety issues of LPs are discussed. This review provides valuable updated information and inspires deeper insights for the large scale development and application of LPs.

Preparation, structural characterization, bioactivities, and applications of Crataegus spp. polysaccharides: A review.

Crataegus, is a genus within the Rosaceae family. It is recognized as a valuable plant with both medicinal and edible qualities, earning it the epithet of the "nutritious fruit" owing to its abundant bioactive compounds. Polysaccharides are carbohydrate polymers linked by glycosidic bonds, one of the crucial bioactive ingredients of Crataegus spp. Recently, Crataegus spp. polysaccharides (CPs) have garnered considerable attention due to their diverse range of bioactivities, including prebiotic, hypolipidemic, anticancer, antibacterial, antioxidant, and immunobiological properties. Herein, we provide a comprehensive overview of recent research on CPs. The analysis revealed that CPs exhibited a broad molecular weight distribution, ranging from 5.70 Da to 4.76 × 108 Da, and are composed of various monosaccharide constituents such as mannose, rhamnose, and arabinose. Structure-activity relationships demonstrated that the biological function of CPs is closely associated with their molecular weight, galacturonic acid content, and chemical modifications. Additionally, CPs have excellent bioavailability, biocompatibility, and biodegradability, which make them promising candidates for applications in the food, medicine, and cosmetic industries. The article also scrutinized the potential development and future research directions of CPs. Overall, this article provides comprehensive knowledge and underpinnings of CPs for future research and development as therapeutic agents and multifunctional food additives.

The potential, challenges, and prospects of the genus Spirulina polysaccharides as future multipurpose biomacromolecules.

Spirulina has been widely used worldwide as a food and medicinal ingredient for centuries. Polysaccharides are major bioactive constituents of Spirulina and are of interest because of their functional properties and unlimited application potential. However, the clinical translation and market industrialization of the polysaccharides from genus Spirulina (PGS) are retarded due to the lack of a further understanding of their isolation, bioactivities, structure-activity relationships (SARs), toxicity, and, most importantly, versatile applications. Herein, we provide an overview of the extraction, purification, and structural features of PGS; meanwhile, the advances in bioactivities, SARs, mechanisms of effects, and toxicity are discussed and summarized. Furthermore, the applications, potential developments, and future research directions are scrutinized and highlighted. This review may help fill the knowledge gap between theoretical insights and practical applications and guide future research and industrial application of PGS.

Comparative analysis of chloroplast genome and new insights into phylogenetic relationships of Ajuga and common adulterants.

Introduction: The potential contamination of herbal medicinal products poses a significant concern for consumer health. Given the limited availability of genetic information concerning Ajuga species, it becomes imperative to incorporate supplementary molecular markers to enhance and ensure accurate species identification. Methods: In this study, the chloroplast (cp) genomes of seven species of the genus Ajuag were sequenced, de novo assembled and characterized. Results: exhibiting lengths ranging from 150,342 bp to 150,472 bp, encompassing 86 - 88 protein-coding genes (PCGs), 35 - 37 transfer RNA, and eight ribosomal RNA. The repetitive sequences, codon uses, and cp genomes of seven species were highly conserved, and PCGs were the reliable molecular markers for investigating the phylogenetic relationship within the Ajuga genus. Moreover, four mutation hotspot regions (accD-psaI, atpH-atpI, ndhC-trnV(UAC), and ndhF-rpl23) were identified within cp genomes of Ajuga, which could help distinguish A. bracteosa and its contaminants. Based on cp genomes and PCGs, the phylogenetic tree preliminary confirmed the position of Ajuga within the Lamiaceae family. It strongly supported a sister relationship between Subsect. Genevense and Subsect. Biflorae, suggesting the merger of Subsect. Biflorae and Subsect. Genevenses into one group rather than maintaining separate categorizations. Additionally, molecular clock analysis estimated the divergence time of Ajuga to be around 7.78 million years ago. Discussion: The species authentication, phylogeny, and evolution analyses of the Ajuga species may benefit from the above findings.

Extraction, structural-activity relationships, bioactivities, and application prospects of Bletilla striata polysaccharides as ingredients for functional products: A review.

Bletilla striata is a well-known medicinal plant with high pharmaceutical and ornamental values. Polysaccharide is the most important bioactive ingredient in B. striata and has various health benefits. Recently, B. striata polysaccharides (BSPs) have attracted much attention from industries and researchers due to their remarkable immunomodulatory, antioxidant, anti-cancer, hemostatic, anti-inflammatory, anti-microbial, gastroprotective, and liver protective effects. Despite the successful isolation and characterization of BSPs, there is still limited knowledge regarding their structure-activity relationships (SARs), safety concerns, and applications, which hinders their full utilization and development. Herein, we provided an overview of the extraction, purification, and structural features, as well as the effects of different influencing factors on the components and structures of BSPs. We also highlighted and summarized the diversity of chemistry and structure, specificity of biological activity, and SARs of BSP. The challenges and opportunities of BSPs in the food, pharmaceutical, and cosmeceutical fields are discussed, and the potential development and future study direction are scrutinized. This article provides comprehensive knowledge and underpinnings for further research and application of BSPs as therapeutic agents and multifunctional biomaterials.