Chemical biology & drug design最新文献

筛选
英文 中文
Antiproliferation and apoptosis studies of estrone pharmacophores in triple-negative breast cancer 雌激素药效团在癌症三阴性乳腺癌中的抗增殖和凋亡研究。
Chemical biology & drug design Pub Date : 2023-07-27 DOI: 10.1111/cbdd.14303
Felix Acheampong, Trevor Ostlund, Mater Mahnashi, Fathi Halaweish
{"title":"Antiproliferation and apoptosis studies of estrone pharmacophores in triple-negative breast cancer","authors":"Felix Acheampong,&nbsp;Trevor Ostlund,&nbsp;Mater Mahnashi,&nbsp;Fathi Halaweish","doi":"10.1111/cbdd.14303","DOIUrl":"10.1111/cbdd.14303","url":null,"abstract":"<p>Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that shows high metastatic capability and poor prognosis. The aggressive behavior of TNBC may involve amplified EGFR expression. Currently, no targeted therapy has been approved for treating TNBC, which urgently needs novel treatment options. In this study, we report that estrone analogs with novel pharmacophores exhibited high potency toward TNBC cells through multiple mechanisms, inhibition of cell proliferation via EGFR receptor, and induction of mitochondrial apoptosis. Molecular docking studies revealed that hit analogs MMA307 and MMA321 were potent against the EGFR receptor (pdb code: 1M17) in silico and were over 10-fold more potent than sorafenib (positive control) when dosed against MDA-MB-468 cells in vitro. MMA307 and MMA321 induced mitochondrial apoptosis as characterized by condensed nuclei with fragmented chromatin, phosphatidylserine flip and modulated expressions of Apaf1, cytochrome c, and caspases 3 and 9. MMA307 and MMA321 inhibited TNBC proliferation through suppression of EGFR and activated EGFR (Y1068) expressions. Similarly, EGFR signaling pathways, RAF/ERK and AKT/mTOR, were inhibited as pARaf, pERK1/2 (characterizes RAF/ERK pathway) and pAKT, pmTOR, p70S6Kα (characterizes AKT/mTOR pathway) were all suppressed. Moreover, MMA307 and MMA321 inhibited TNBC cell growth through downregulation of cyclin D1 expression and arresting TNBC cells in the G<sub>1</sub> phase of cell cycle. This study reports for the first time that estrone congeners with novel pharmacophores may be an effective therapy for TNBC. Findings from this research provide a solid foundation for further preclinical and clinical studies in developing estrone derivatives as novel TNBC therapeutics.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"102 5","pages":"1050-1066"},"PeriodicalIF":0.0,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9937662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
The evaluation of isatin analogues as inhibitors of monoamine oxidase 靛蓝类似物作为单胺氧化酶抑制剂的评价。
Chemical biology & drug design Pub Date : 2023-07-27 DOI: 10.1111/cbdd.14304
Izak F. Prinsloo, Jacobus P. Petzer, Theunis T. Cloete, Anél Petzer
{"title":"The evaluation of isatin analogues as inhibitors of monoamine oxidase","authors":"Izak F. Prinsloo,&nbsp;Jacobus P. Petzer,&nbsp;Theunis T. Cloete,&nbsp;Anél Petzer","doi":"10.1111/cbdd.14304","DOIUrl":"10.1111/cbdd.14304","url":null,"abstract":"<p>The small molecule, isatin, is a well-known reversible inhibitor of the monoamine oxidase (MAO) enzymes with IC<sub>50</sub> values of 12.3 and 4.86 μM for MAO-A and MAO-B, respectively. While the interaction of isatin with MAO-B has been characterized, only a few studies have explored structure–activity relationships (SARs) of MAO inhibition by isatin analogues. The current study therefore evaluated a series of 14 isatin analogues as in vitro inhibitors of human MAO-A and MAO-B. The results indicated good potency MAO inhibition for some isatin analogues with five compounds exhibiting IC<sub>50</sub> &lt; 1 μM. 4-Chloroisatin (<b>1b</b>) and 5-bromoisatin (<b>1f</b>) were the most potent inhibitors with IC<sub>50</sub> values of 0.812 and 0.125 μM for MAO-A and MAO-B, respectively. These compounds were also found to be competitive inhibitors of MAO-A and MAO-B with K<sub>i</sub> values of 0.311 and 0.033 μM, respectively. Among the SARs, it was interesting to note that C5-substitution was particularly beneficial for MAO-B inhibition. MAO inhibitors are established drugs for the treatment of neuropsychiatric and neurodegenerative disorders, while potential new roles in prostate cancer and cardiovascular disease are being investigated.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"102 5","pages":"1067-1074"},"PeriodicalIF":0.0,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.14304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9883586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Praeruptorin A inhibits the activation of NF-κB pathway and the expressions of inflammatory factors in poly (I:C)-induced RAW264.7 cells 前胡素A抑制poly(I:C)诱导的RAW264.7细胞中NF-κB通路的激活和炎症因子的表达。
Chemical biology & drug design Pub Date : 2023-07-27 DOI: 10.1111/cbdd.14310
Jiayan Hu, Roujun Liu, Zhouxin Yang, Xinyu Pan, Yuanjing Li, Yanghui Gong, Dongyang Guo
{"title":"Praeruptorin A inhibits the activation of NF-κB pathway and the expressions of inflammatory factors in poly (I:C)-induced RAW264.7 cells","authors":"Jiayan Hu,&nbsp;Roujun Liu,&nbsp;Zhouxin Yang,&nbsp;Xinyu Pan,&nbsp;Yuanjing Li,&nbsp;Yanghui Gong,&nbsp;Dongyang Guo","doi":"10.1111/cbdd.14310","DOIUrl":"10.1111/cbdd.14310","url":null,"abstract":"<p>Praeruptorin A (PA), a natural coumarin compound, has significant anti-inflammatory effects. In this study, we evaluate the anti-inflammatory effect of PA on RAW 264.7 mouse macrophages induced by Polyinosinic acid-polycytidylic acid (poly (I:C)). RAW 264.7 mouse macrophages induced by poly (I:C) were treated with or without PA, the viability of which was determined to screen working solution of PA. RNA-sequencing was applied to analyze the differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out. The expressions of interleukin (IL)-1β, heme oxygenase 1 (HMOX1), prostaglandin-endoperoxide synthase 2 (PTGS2), ATP binding cassette subfamily A member 1 (Abca1) and NF-κB-related proteins were measured by enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. As a result, PA at 1, 2, 3, 4 and 5 μM slightly affected cell viability, while PA at 6 and 7 μM significantly inhibited cell viability. GO and KEGG analysis results revealed that DEGs were mainly enriched in the pathways related to inflammatory signaling. Through further analysis, we obtained five possible targets of PA, and verified that PA inhibited the expressions of IL-1β, HMOX1, PTGS2 and Abca1 as well as the activation of NF-κB pathway in poly (I:C)-induced RAW264.7 cells. To summarize, PA may inhibit expressions of the inflammation-related genes in poly (I:C)-induced RAW264.7 cells, which demonstrates its potential as a drug against virus related diseases.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"102 5","pages":"1110-1120"},"PeriodicalIF":0.0,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9937663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Isolation and purifications of an ambuic acid derivative compound from marine algal endophytic fungi Talaromyces flavus that induces apoptosis in MDA-MB-231 cancer cells 从海藻内生真菌Talaromyces flavus中分离和纯化一种诱导MDA-MB-231癌症细胞凋亡的ambuic酸衍生物化合物。
Chemical biology & drug design Pub Date : 2023-05-29 DOI: 10.1111/cbdd.14271
Ramalingam Parthasarathy, Damodaran Sruthi, Chelliah Jayabaskaran
{"title":"Isolation and purifications of an ambuic acid derivative compound from marine algal endophytic fungi Talaromyces flavus that induces apoptosis in MDA-MB-231 cancer cells","authors":"Ramalingam Parthasarathy,&nbsp;Damodaran Sruthi,&nbsp;Chelliah Jayabaskaran","doi":"10.1111/cbdd.14271","DOIUrl":"10.1111/cbdd.14271","url":null,"abstract":"<p>In recent years, there has been a lot of buzz about the possibilities of marine microflora as a source of new therapeutic drugs. The strong anti-tumor potency of compounds found in marine resources reflects the ocean's enormous potential as a source of anticancer therapeutics. In this present investigation, an ambuic acid derivative anticancer compound was isolated from <i>Talaromyces flavus</i>, and its cytotoxicity and apoptosis induction potential were analyzed. <i>T. flavus</i> was identified through morphological and molecular analysis. The various organic solvent extracts of <i>T. flavus</i> grown on different growth mediums were evaluated for cytotoxicity on different cancer cell lines. The potent cytotoxicity was shown in the ethyl acetate extract of a fungal culture grown in the M1-D medium for 21 days. Furthermore, the anticancer compound was identified using preparative thin layer chromatography, followed by its purification in significant proportions using column chromatography. The spectroscopic and chromatographic analysis revealed that the structure of the purified molecules was an ambuic acid derivative. The ambuic acid derivative compound showed potent cytotoxicity on MDA-MB-231 (breast cancer cells) with an IC<sub>50</sub> value of 26 μM and induced apoptosis in the MDA-MB-231 cells in a time-dependent and reactive oxygen species-independent manner.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"102 5","pages":"1308-1326"},"PeriodicalIF":0.0,"publicationDate":"2023-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10197579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信