Chemical & pharmaceutical bulletin最新文献

{"title":"Identification of a Novel Retinoid X Receptor Agonist from Boenninghausenia albiflora var. japonica.","authors":"Ryura Tateiwa, Yudai Nakama, Ayaka Murase, Tomoki Mizoguchi, Makoto Inoue, Ken-Ichi Nakashima","doi":"10.1248/cpb.c24-00728","DOIUrl":"https://doi.org/10.1248/cpb.c24-00728","url":null,"abstract":"<p><p>Retinoid X receptors (RXRs) are nuclear receptors involved in various crucial biological processes, such as gene regulation, metabolism, and cell differentiation. They predominantly function as heterodimers with other nuclear receptors and modulate gene expression in response to ligand binding. Additionally, they act as therapeutic targets for different conditions, such as cancer and metabolic disorders. Although synthetic RXR agonists, such as bexarotene, are used in clinical settings, they exert adverse side effects. In this study, to explore insights into potential natural RXR agonists as alternatives to existing drugs, we isolated 14 coumarins, including 1 new compound from Boenninghausenia albiflora var. japonica (Rutaceae). Among them, daphnoretin methyl ether (14), a known biscoumarin, was found to exhibit subtype-nonspecific RXR agonist activity.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"173-178"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Acidic Triterpenoid Saponins from Silene vulgaris Using a Methylation-Based Isolation and LC-MS Analysis Strategy.","authors":"Takashi Kikuchi, Danyang Liu, Kouharu Otsuki, Kazuo Koike, Wei Li","doi":"10.1248/cpb.c24-00809","DOIUrl":"https://doi.org/10.1248/cpb.c24-00809","url":null,"abstract":"<p><p>The Silene genus plants in the Caryophyllaceae family are a large genus with over 850 species. It has been known that Silene genus plants contain triterpenoid saponins. These saponins have glucuronic acid in the sugar chain and are difficult to separate in chromatography. In this study, a strategy was developed to clarify the distribution of triterpenoid saponins in whole plants of Silene vulgaris by isolation of neutralized saponins using methylation reactions, which were used as standard substances for LC-MS analysis, and elucidating their characteristic MS and MS/MS fragment patterns. The n-butanol fraction of the methanol extract from the whole plant of S. vulgaris was separated to obtain fractions including saponins by octadecyl silica column chromatography. Then, each fraction was treated with trimethylsilyl diazomethane for methylation of the carboxyl groups of glucuronic acid in the molecules, and five triterpenoid methylated saponins (7a, 13a, 14a, 16a, and 17a) were isolated using HPLC. The chemical structures of the isolated compounds were determined by spectroscopic analyses including NMR and MS, and their characteristic fragmentations were also clarified in LC-MS and MS/MS. It was performed on the n-butanol fraction from the whole plant of S. vulgaris, and the chemical structures of 22 triterpenoid saponins were estimated based on the MS and MS/MS fragmentation patterns of the isolated triterpenoid saponins.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"179-188"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoflavone Constituents of the Underground Parts of Iris florentina and Their Inhibitory Activity on the Formation of Advanced Glycation End Products.","authors":"Yuka Yoshizawa, Nana Fujita, Akihito Yokosuka, Yoshihiro Mimaki","doi":"10.1248/cpb.c24-00776","DOIUrl":"https://doi.org/10.1248/cpb.c24-00776","url":null,"abstract":"<p><p>Two new isoflavone glucosides, irisolone 4'-O-[O-β-d-glucopyranosyl-(1→6)-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside] (1) and iriskashmirianin 4'-O-[O-β-d-glucopyranosyl-(1→6)-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside] (2) were isolated from the underground parts of Iris florentina (Iridaceae). The structures of 1 and 2 were determined based on extensive spectroscopic data analyses and hydrolytic cleavage results. The isoflavone derivatives previously isolated from this plant were evaluated for their ability to inhibit the formation of advanced glycation end products.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"168-172"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation and Identification of Three New Iridoid Glucosides from the Aerial Parts of Paederia scandens.","authors":"Masashi Fukaya, Kaori Ryu, Tetsuro Ito","doi":"10.1248/cpb.c24-00777","DOIUrl":"https://doi.org/10.1248/cpb.c24-00777","url":null,"abstract":"<p><p>Sulfur-containing compounds are found in various medicinal products, where they play crucial roles in biological activities such as antimicrobial, anticancer, and other therapeutic effects. These compounds are commonly found in species of Allium, especially onions and garlic; however, there is little evidence of their presence in other plants. In particular, sulfur-containing iridoid glycosides with anticancer properties, which are very promising compounds as pharmaceutical seeds, have been isolated from Paederia scandens (Rubiaceae), also known as the skunk vine because of its strong smell caused by methyl mercaptan. Herein, we describe the isolation and structural elucidation of 3 new iridoid glycosides from the aerial parts of P. scandens. Their biosynthetic pathways are also discussed.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"156-161"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthetic Studies on Vitamin D Derivatives with Diverse but Selective Biological Activities.","authors":"Atsushi Kittaka","doi":"10.1248/cpb.c24-00598","DOIUrl":"https://doi.org/10.1248/cpb.c24-00598","url":null,"abstract":"<p><p>2α-Functionalization of 1α,25-dihydroxyvitamin D₃ (active vitamin D₃) A-ring enhances binding affinity for the vitamin D receptor (VDR) and prolongs the half-life in target cells due to gaining resistance to CYP24A1-dependant metabolism. The wide variety of modified A-ring precursor enynes for Trost coupling with CD-ring bromoolefin were synthesized from d-glucose. The A-ring modification provided potent, selective biological activities without calcemic side-effects in vivo; for example, 2α-(3-hydroxypropyl)-19-nor-1α,25-dihydroxyvitamin D₃ (MART-10) exhibits potent antitumor activity (0.3µg/kg/d, twice/week for 3 weeks) in nude mice inoculated with BxpC-3 cancer cells, 2α-[2-(tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D₃ (AH-1) shows better bone-forming effects (0.02µg/kg/d, 5d/week for 4 weeks) in ovariectomized (OVX) rats as an osteoporosis model than natural active vitamin D₃, and NS-74c exhibits potent VDR-antagonistic activity (IC₅₀ 7.4pM) in HL-60 culture cells. The A-ring modification was also applicable to the synthesis of stable 14-epi-19-nortachysterols, and their novel VDR binding mode was confirmed by X-ray co-crystallographic analysis. 25-Hydroxyvitamin D₃ has two independent target molecules: VDR and a sterol regulatory element-binding protein (SREBP)/SREBP cleavage-activating protein (SCAP) complex, and 25-hydroxyvitamin D₃ shows SREBP/SCAP inhibitory activity. The VDR-silent vitamin D analog KK-052 with selective SREBP/SCAP inhibitory activity in vivo was developed. A chemical library of side-chain fluorinated vitamin D analogs is currently under construction, and some analogs have shown potent anti-inflammatory activity and therapeutic effects on psoriasis model mice.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 1","pages":"1-17"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Mixing Characteristics of Magnesium Stearate Using Triboelectric Properties.","authors":"Kenta Fujinuma, Masataka Ito, Etsuo Yonemochi, Katsuhide Terada, Hironori Suzuki, Shuji Noguchi","doi":"10.1248/cpb.c24-00694","DOIUrl":"10.1248/cpb.c24-00694","url":null,"abstract":"<p><p>Magnesium stearate (MgSt), which is often used as a lubricant in the production of solid formulations, has different stearic acid and palmitic acid contents depending on the lot and manufacturer, resulting in differences in mixability and lubricating effect. However, there are few reports on the effect of the different physical properties of MgSt samples on mixing and tablet formation. Additionally, it is known that the triboelectric properties of components affect the mixability. Overmixing of formulations can decrease tablet hardness. In this study, the triboelectric properties and mixability of MgSt samples with different lots and manufacturers were evaluated. Tablet hardness was used as an index of the mixability of the MgSt samples with various excipients. The triboelectric properties of the MgSt samples depended on the production lot. Mixability was higher when the triboelectric properties of the excipient and MgSt were different. By evaluating the charge properties of MgSt, it should be possible to select the optimum lot and manufacturer of MgSt for specific formulations.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 2","pages":"78-85"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereoselective Synthesis of Aromatic Polyketide Prealnumycin.","authors":"Kei Kitamura, Taiki Yamasaki, Hiroto Kaku","doi":"10.1248/cpb.c24-00781","DOIUrl":"10.1248/cpb.c24-00781","url":null,"abstract":"<p><p>Prealnumycin (1), a benzoisochromanequinone compound, produces biologically active exfoliamycin or alnumycin through hybridization with D-ribose or oxidation. We report herein a concise and stereoselective synthesis of 1. The anionic annulation of phthalide 5 with enone 6, prepared via a transition metal-catalyzed enantioselective route, afforded tricyclic lactone 4. This intermediate then underwent a highly diastereoselective introduction of an n-propyl group through nucleophilic addition followed by silane reduction. Subsequent regioselective arene oxidation of 18 using cerium(IV) ammonium nitrate (CAN) afforded naphthoquinone 2. Further manipulations, including acidic deprotection and elimination, yielded prealnumycin in 8 steps.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 2","pages":"86-93"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Structure-Activity Relationships of Novel Benzofuran Derivatives with Osteoblast Differentiation-Promoting Activity.","authors":"Masafumi Ando, Shota Kawai, Ko Morishita, Shunsuke Takashima, Kazuya Otake, Megumi Yamamoto, Yoshimichi Shoji, Eiichi Hinoi, Tatsuya Kitao, Hiroaki Shirahase","doi":"10.1248/cpb.c24-00664","DOIUrl":"10.1248/cpb.c24-00664","url":null,"abstract":"<p><p>Osteoporosis is caused by an imbalance between bone resorption and formation, which decreases bone mass and strength and increases the risk of fracture. Therefore, osteoporosis is treated with oral resorption inhibitors, such as bisphosphonates, and parenteral osteogenic drugs, including parathyroid hormone and antisclerostin antibodies. However, orally active osteogenic drugs have not yet been developed. In the present study, to find novel candidates for oral osteogenic drugs, various benzofuran derivatives were synthesized and their effects on osteoblast differentiation were examined in mouse mesenchymal stem cells (ST2 cells). Among the compounds tested, 3-{4-[2-(2-isopropoxyethoxy)ethoxy]phenyl}benzofuran-5-carboxamide (23d) exhibited potent osteoblast differentiation-promoting activity, estimated as EC₂₀₀ for increasing alkaline phosphatase activity, and good oral absorption in female rats, resulting in high C_max/EC₂₀₀. Dual-energy X-ray absorptiometry scanning revealed that 23d at 10 mg/kg/d for 8 weeks increased femoral bone mineral density in ovariectomized rats with an elevation in plasma bone-type alkaline phosphatase activity, and micro-computed tomography showed that it increased bone volume, mineral contents, and strength in femoral diaphysis cortical, but not trabecular bone during the experiment period. 23d potently inhibited cyclin-dependent kinase 8 (CDK8) activity, suggesting that its osteoblastogenic activity is mediated by the suppression of CDK8, as previously reported for diphenylether derivatives. In conclusion, the structure-activity relationships of novel benzofuran derivatives were clarified and 3,5-disubstituted benzofuran was identified as a useful scaffold for orally active osteogenic compounds. Compound 23d exhibited potent osteoblastogenic activity through CDK8 inhibition and osteogenic effects in ovariectomized rats, indicating its potential as an orally active anti-osteoporotic drug.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 1","pages":"25-38"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ion-Pair Extraction with Tetracyanocyclopentadienides: A Method for Estimating Extraction Efficiency.","authors":"Takeo Sakai, Masanari Ota, Miho Ito, Riho Miura, Yuto Fumimoto, Yuji Mori","doi":"10.1248/cpb.c24-00630","DOIUrl":"10.1248/cpb.c24-00630","url":null,"abstract":"<p><p>Ion-pair extraction with tetracyanocyclopentadienides (TCCPs) is an effective method for isolating ammonium cations; however, predicting the extractability of ammonium-TCCP ion pairs is challenging. Herein, the measured extraction coefficients (LogK_ex) of ammonium-TCCP ion pairs allowed the values of A (an index for anion extractability) for the TCCP anions to be determined (-3.1 to -1.4); these values were higher than and similar to those of perchlorate and picrate anions, respectively. The correlation between LogK_ex and the sum of the values of A and the calculated Log P of ammonium cations revealed that LogK_ex can be estimated by the equation LogK_ex = A + CLOGP_NR4 + 1.6, where CLOGP_NR4 is the CLOGP value obtained using the \"no-plus\" ammonium structure. The LogK_ex value can be used to predict the extractability of quaternary ammonium ions.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 2","pages":"121-135"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guided Isolation of Isopentenyl Flavonoids from Daphne giraldii Based on the Combination of GNPS and SMART.","authors":"Bo-Yuan Zhao, Ben-Song Xin, Shuang Qiu, Guo-Dong Yao, Xiao-Xiao Huang, Shao-Jiang Song","doi":"10.1248/cpb.c24-00462","DOIUrl":"https://doi.org/10.1248/cpb.c24-00462","url":null,"abstract":"<p><p>Six flavonoids (1-6), including 3 previously undescribed compounds (1-3), were isolated from the dried roots and stem skins of Daphne giraldii Nitsche. The strategy of LC-tandem mass spectrometry-based Global Natural Products Social Molecular Networking (GNPS) molecular network technology and NMR-based Small Molecule Accurate Recognition Technology (SMART) technology facilitated the precise separation of isopentenyl flavonoids in D. giraldii. The structures were determined through comprehensive spectroscopic analysis. Furthermore, all compounds were evaluated for their cytotoxic activity against Hep3B cells. Specifically, compounds 1 and 3 exhibited significant cytotoxicity with IC₅₀ values of 5.52 ± 0.57 and 2.53 ± 0.49 μM, respectively, compared to the positive control sorafenib (IC₅₀ = 7.08 ± 0.23 μM).</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"189-194"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}