Chemical biology & drug design最新文献_第2页

Curcumin inhibits malignant behavior of colorectal cancer cells by regulating M2 polarization of tumor-associated macrophages and metastasis associated in colon cancer 1 (MACC1) expression 姜黄素通过调节肿瘤相关巨噬细胞M2极化和结肠癌转移相关的癌症1（MACC1）表达来抑制结直肠癌癌症细胞的恶性行为。

Chemical biology & drug design Pub Date : 2023-08-20 DOI: 10.1111/cbdd.14330

Shuke Ge, Xu Sun, Limin Sang, Min Zhang, Xubo Yan, Qi Ju, Xuefeng Ma, Meng Xu

{"title":"Curcumin inhibits malignant behavior of colorectal cancer cells by regulating M2 polarization of tumor-associated macrophages and metastasis associated in colon cancer 1 (MACC1) expression","authors":"Shuke Ge, Xu Sun, Limin Sang, Min Zhang, Xubo Yan, Qi Ju, Xuefeng Ma, Meng Xu","doi":"10.1111/cbdd.14330","DOIUrl":"10.1111/cbdd.14330","url":null,"abstract":"The present study was to investigate the underlying mechanism of the antitumor effect of curcumin in colorectal cancer cells, focusing on the M2 polarization of tumor-associated macrophages (TAMs). The effect of curcumin on the malignant behavior of colorectal cancer cells was investigated by WST assay for cell growth, and Transwell assay for cell migration/invasion. THP-1 cells were differentiated into macrophages and coculture with colorectal cancer cells to study the influence of curcumin on M2 polarization, presenting as the levels of ARG1 mRNA, IL-10, and CD163-positive cells. GEO database was searched for the shared altered gene of curcumin in colorectal cells and human monocytes. Molecular docking was used to visualize the binding between curcumin and MACC1. Curcumin restricted the proliferation, apoptosis, and migration/invasion of HCT 116 and SW620 cells. Curcumin attenuated levels of the M2 macrophage markers, CD163 + cells, IL-10 secretion, and ARG1 mRNA. MACC1 was a target of curcumin in colorectal cancer cells, relating to macrophage. Rescue experiments showed that MACC1 overexpression can reverse the antitumor effect of curcumin in colorectal cancer cells and M2 polarization of TAMs. Curcumin's antiproliferative and anti-migratory effects in colorectal cancer cells may be mediated by MACC1 and inhibition of M2 polarization of TAMs.","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"102 5","pages":"1202-1212"},"PeriodicalIF":0.0,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10031951","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

Elucidation of the mechanisms and molecular targets of KeChuanLiuWei-Mixture for treatment of severe asthma based on network pharmacology 基于网络药理学阐明咳喘六味合剂治疗重症哮喘的作用机制和分子靶点。

Chemical biology & drug design Pub Date : 2023-08-13 DOI: 10.1111/cbdd.14302

Yanqi Cheng, Ding Sun, Lu Zou, Shaobin Li, Ling Tang, Xiao Yu, Binqing Tang, Yingen Wu, Hong Fang

{"title":"Elucidation of the mechanisms and molecular targets of KeChuanLiuWei-Mixture for treatment of severe asthma based on network pharmacology","authors":"Yanqi Cheng, Ding Sun, Lu Zou, Shaobin Li, Ling Tang, Xiao Yu, Binqing Tang, Yingen Wu, Hong Fang","doi":"10.1111/cbdd.14302","DOIUrl":"10.1111/cbdd.14302","url":null,"abstract":"KeChuanLiuWei-Mixture (KCLW) is widely used as a Chinese medicine prescription to treat severe asthma. However, the underlying therapeutic mechanism of KCLW remains unclear. In this study, a network pharmacology method was used to identify the chemical constituents of KCLW by the TCMSP database and ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry. Differential expression identification, protein–protein interaction (PPI) network and functional enrichment analysis were used to screen key targets of KCLW for severe asthma. Our results confirmed that quercetin, luteolin, kaempferol, and wogonin are the most critical active ingredients in KCLW. Moreover, the 16 relevant severe asthma-related targets of KCLW were obtained by overlapping the PPI networks of the KCLW putative targets and severe asthma-related genes, among which the most important targets were IL-6, NOS2, VEGFA, CXCL2, and PLAT. Functionally, the 16-targets and their interacting differentially expressed genes were primarily related to biological functions and pathways related to immunity and inflammation, such as inflammatory response, T cell differentiation, Nrf2/HO-1 signaling pathway, TGF-β/Smad signaling pathway, and NF-κB signaling pathway. KCLW inhibited inflammation in PDGF-BB-induced airway smooth muscle cells. In summary, this study demonstrates the active substance and potential therapeutic mechanism of KCLW in severe asthma, and offers a clinical direction for KCLW against severe asthma.","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"102 5","pages":"1034-1049"},"PeriodicalIF":0.0,"publicationDate":"2023-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9981507","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

A novel alpha-amylase inhibitor-based spirooxindole-pyrrolidine-clubbed thiochromene-pyrzaole pharmacophores: Unveiling the [3+2] cycloaddition reaction by molecular electron density theory 一种新的基于α-淀粉酶抑制剂的螺环吲哚-吡咯烷棒状硫铬酮-吡喃酮药效团：用分子电子密度理论揭示[3+2]环加成反应。

Chemical biology & drug design Pub Date : 2023-08-10 DOI: 10.1111/cbdd.14299

Mohammad Shahidul Islam, Abdullah Mohammed Al-Majid, Matti Haukka, Zahida Parveen, Nabeela Ravaiz, Abdul Wadood, Ashfaq Ur Rehman, Mar Ríos-Gutiérrez, Luis R. Domingo, Assem Barakat

{"title":"A novel alpha-amylase inhibitor-based spirooxindole-pyrrolidine-clubbed thiochromene-pyrzaole pharmacophores: Unveiling the [3+2] cycloaddition reaction by molecular electron density theory","authors":"Mohammad Shahidul Islam, Abdullah Mohammed Al-Majid, Matti Haukka, Zahida Parveen, Nabeela Ravaiz, Abdul Wadood, Ashfaq Ur Rehman, Mar Ríos-Gutiérrez, Luis R. Domingo, Assem Barakat","doi":"10.1111/cbdd.14299","DOIUrl":"10.1111/cbdd.14299","url":null,"abstract":"A novel spirooxindole-pyrrolidine clubbed thiochromene and pyrazole motifs were synthesized by [3+2] cycloaddition (32CA) reactions in one step process starting from the ethylene-based thiochromene and pyrazole scaffolds with the secondary amino-acids and substituted isatins in high yield. The 32CA reaction of AY 10 with ethylene derivative 6 has also been studied with Molecular Electron Density Theory. The high nucleophilic character of AY 10, N = 4.39 eV, allows explaining that the most favorable TS-on is 13.9 kcal mol−1 below the separated reagent. This 32CA, which takes place through a non-concerted one-step mechanism, presents a total ortho regio- and endo stereoselectivity, which is controlled by the formation of two intramolecular H…O hydrogen bonds. The design of spirooxindole-pyrrolidines engrafted thiochromene and pyrazole was tested for alpha-amylase inhibition and show a high efficacy in nanoscale range of reactivity. The key interaction between the most active hybrids and the receptor was studied by molecular docking. The physiochemical properties of the designed spirooxindole-pyrrolidines were carried out by in silico ADMET prediction. The newly synthesized most potent hybrid could be considered as a lead compound for drug discovery development for type 2 diabetes mellitus (T2DM).","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"102 5","pages":"972-995"},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10102934","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: 2

Evaluation of linagliptin and insulin combined therapy on unfolded protein response in type 1 diabetic mouse heart 利格列汀和胰岛素联合治疗对1型糖尿病小鼠心脏未折叠蛋白反应的评价。

Chemical biology & drug design Pub Date : 2023-08-02 DOI: 10.1111/cbdd.14308

Züleyha Doğanyiğit, Aslı Okan, Serpil Taheri, Zeynep Yılmaz, Enes Akyüz, Necdet Demir

{"title":"Evaluation of linagliptin and insulin combined therapy on unfolded protein response in type 1 diabetic mouse heart","authors":"Züleyha Doğanyiğit, Aslı Okan, Serpil Taheri, Zeynep Yılmaz, Enes Akyüz, Necdet Demir","doi":"10.1111/cbdd.14308","DOIUrl":"10.1111/cbdd.14308","url":null,"abstract":"The aim of this study is to reveal the effects of the use of linagliptin, a DPP-4 inhibitor due to its beneficial cardiovascular effects, on endoplasmic reticulum stress (ERS) signaling, which is involved in the pathogenesis of cardiovascular complications related to type 1 diabetes. BALB/c female mice (n = 72) were divided into six groups: control, diabetes+insulin, diabetes+linagliptin, diabetes+linagliptin+insulin, diabetes+TUDCA, and diabetes+TUDCA+insulin. Immunohistochemistry and western blot method, qRT-PCR, ELISA method, and malondialdehyde (MDA) measurements were performed. Linagliptin administered to the type 1 diabetic mouse heart significantly reduced the expression levels of the total and cleaved forms of ATF6, ATF4, and p-JNK, caspase 3. Immunohistochemical and western blot analyses revealed that cleaved caspase 3 protein expression was significantly increased in the diabetes+insulin group compared to the other groups. According to ELISA findings, TUDCA was more effective in reducing NOX 1 and MDA levels than linagliptin. While linagliptin decreased the Chop mRNA level, no change was observed in the Grp78 mRNA level. Our findings showed that there was not much difference between the administration of linagliptin alone or in combination with insulin. Our study reveals that linagliptin is an effective therapeutic agent on ERS and apoptotic UPR in type 1 diabetic hearts.","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":"102 5","pages":"1085-1096"},"PeriodicalIF":0.0,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9926987","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

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, Trevor Ostlund, Mater Mahnashi, Fathi Halaweish","doi":"10.1111/cbdd.14303","DOIUrl":"10.1111/cbdd.14303","url":null,"abstract":"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 G1 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.","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, Jacobus P. Petzer, Theunis T. Cloete, Anél Petzer","doi":"10.1111/cbdd.14304","DOIUrl":"10.1111/cbdd.14304","url":null,"abstract":"The small molecule, isatin, is a well-known reversible inhibitor of the monoamine oxidase (MAO) enzymes with IC50 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 IC50 < 1 μM. 4-Chloroisatin (1b) and 5-bromoisatin (1f) were the most potent inhibitors with IC50 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 Ki 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.","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, Roujun Liu, Zhouxin Yang, Xinyu Pan, Yuanjing Li, Yanghui Gong, Dongyang Guo","doi":"10.1111/cbdd.14310","DOIUrl":"10.1111/cbdd.14310","url":null,"abstract":"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.","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, Damodaran Sruthi, Chelliah Jayabaskaran","doi":"10.1111/cbdd.14271","DOIUrl":"10.1111/cbdd.14271","url":null,"abstract":"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 Talaromyces flavus, and its cytotoxicity and apoptosis induction potential were analyzed. T. flavus was identified through morphological and molecular analysis. The various organic solvent extracts of T. flavus 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 IC50 value of 26 μM and induced apoptosis in the MDA-MB-231 cells in a time-dependent and reactive oxygen species-independent manner.","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