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Baicalein, a component of banxia xiexin decoction, alleviates CPT-11-induced gastrointestinal dysfunction by inhibiting ALOX15-mediated ferroptosis. 黄芩苷是板下泻心汤的一种成分,通过抑制ALOX15介导的脱铁性贫血来减轻CPT-11诱导的胃肠道功能障碍。
Chemical biology & drug design Pub Date : 2023-12-01 Epub Date: 2023-09-21 DOI: 10.1111/cbdd.14349
Jingbo Pei, Yuanyuan Zou, Wenying Zhou, Yakun Wang
{"title":"Baicalein, a component of banxia xiexin decoction, alleviates CPT-11-induced gastrointestinal dysfunction by inhibiting ALOX15-mediated ferroptosis.","authors":"Jingbo Pei, Yuanyuan Zou, Wenying Zhou, Yakun Wang","doi":"10.1111/cbdd.14349","DOIUrl":"10.1111/cbdd.14349","url":null,"abstract":"<p><p>Baicalein, one of the active ingredients of banxia xiexin decoction, has good therapeutic efficacy in treating diarrhea and improving gastrointestinal dysfunction. The role and mechanism of Baicalein on irinotecan (CPT-11)-induced gastrointestinal dysfunction are the focus of this study. Concretely, CPT-11 induced delayed diarrhea rat model and intestinal epithelial cell (IEC)-6 cell injury model with Baicalein treatment as needed. Colonic pathological changes were analyzed by hematoxylin-eosin staining, and inflammatory factor expressions in serum were determined by enzyme-linked immunosorbent assay. Immunohistochemistry and western blot were performed to quantify ferroptosis-related protein expressions. Thiobarbituric acid reactive substances (TBARS) kits and colorimetric assay kit were applied to detect lipid peroxidation levels and Fe<sup>2+</sup> content, respectively. In vitro experiments also included quantitative real-time polymerase chain reaction, cell counting kit-8, and C11 BODIPY staining. CPT-11 induced aggravation of intestinal tissue damage, inflammatory factor release, Fe<sup>2+</sup> accumulation, upregulation of lipid peroxidation and 15-Lipoxygenase (ALOX15) expression, and downregulation of glutathione peroxidase 4 (Gpx4) and SLC7A11 in vivo in rats; however, Baicalein dose-dependently reversed the effects of CPT-11. Baicalein elevated cell viability, reduced lipid peroxidation and Fe<sup>2+</sup> accumulation, and elevated Gpx4 and SLC7A11 levels, whereas ALOX15 overexpression reversed the effects of Baicalein on a CPT-11-induced IEC-6 cell injury model. In conclusion, Baicalein plays a mitigating role in CPT-11-induced delayed diarrhea via ALOX15-mediated ferroptosis.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41180705","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
Assessment of the anti-inflammatory mechanism of quercetin 3,7-dirhamnoside using an integrated pharmacology strategy. 采用综合药理学策略评估槲皮素3,7-dirhamnoside的抗炎机制。
Chemical biology & drug design Pub Date : 2023-12-01 Epub Date: 2023-10-08 DOI: 10.1111/cbdd.14346
Xinqian He, Yongzhi Sun, Xiaomeng Lu, Fan Yang, Ting Li, Changsheng Deng, Jianping Song, Xin'an Huang
{"title":"Assessment of the anti-inflammatory mechanism of quercetin 3,7-dirhamnoside using an integrated pharmacology strategy.","authors":"Xinqian He, Yongzhi Sun, Xiaomeng Lu, Fan Yang, Ting Li, Changsheng Deng, Jianping Song, Xin'an Huang","doi":"10.1111/cbdd.14346","DOIUrl":"10.1111/cbdd.14346","url":null,"abstract":"<p><p>Pouzolzia zeylanica (L.) Benn. is a Chinese herbal medicine widely used for its anti-inflammatory and pus-removal properties. To explore its potential anti-inflammatory mechanism, quercetin 3,7-dirhamnoside (QDR), the main flavonoid component of P. zeylanica (L.) Benn., was extracted and purified. The potential anti-inflammatory targets of QDR were predicted using network analysis. These potential targets were verified using molecular docking, molecular dynamics simulations, and in vitro experiments. Consequently, 342 potential anti-inflammatory QDR targets were identified. By analyzing the intersection between the protein-protein interaction and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we identified several potential protein targets of QDR, including RAC-alpha serine/threonine-protein kinase (AKT1), Ras-related C3 botulinum toxin substrate 1 (RAC1), nitric oxide synthase 3 (NOS3), serine/threonine-protein kinase mTOR (mTOR), epidermal growth factor receptor (EGFR), growth factor receptor-bound protein 2 (GRB2), and endothelin-1 receptor (EDNRA). QDR has anti-inflammatory activity and regulates immune responses and apoptosis through chemokines, Phosphatidylinositol 3-kinase 3(PI3K)/AKT, cAMP, T-cell receptor, and Ras signaling pathways. Molecular docking analysis showed that QDR has good binding abilities with AKT1, mTOR, and NOS3. In addition, molecular dynamics simulations demonstrated that the protein-ligand complex systems formed between QDR and AKT1, mTOR, and NOS3 have high dynamic stability, and their protein-ligand complex systems possess strong binding ability. In RAW264.7 macrophages, QDR significantly inhibited lipopolysaccharides (LPS)-induced inducible nitric oxide synthase expression, nitric oxide (NO) release and the generation of proinflammatory cytokines IL-6, IL-1β, and TNF-α. QDR downregulated the expression of p-AKT1(Ser473)/AKT1 and p-mTOR (Ser2448)/mTOR, and upregulated the expression of NOS3, Rictor, and Raptor. This indicates that the anti-inflammatory mechanisms of QDR involve regulation of AKT1 and mTOR to prevent apoptosis and of NOS3 which leads to the release of endothelial NO. Thus, our study elucidated the potential anti-inflammatory mechanism of QDR, the main flavonoid found in P. zeylanica (L.) Benn.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41165104","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
Design and synthesis of novel 1,2,3,4-tetrazines as new anti-leukemia cancer agents 新型抗白血病癌症药物1,2,3,4-四嗪的设计与合成。
Chemical biology & drug design Pub Date : 2023-09-20 DOI: 10.1111/cbdd.14328
Oznur Eyilcim, Fulya Gunay, Omer Tahir Gunkara, Yuk Yin Ng, Ozlem Ulucan, Ihsan Erden
{"title":"Design and synthesis of novel 1,2,3,4-tetrazines as new anti-leukemia cancer agents","authors":"Oznur Eyilcim,&nbsp;Fulya Gunay,&nbsp;Omer Tahir Gunkara,&nbsp;Yuk Yin Ng,&nbsp;Ozlem Ulucan,&nbsp;Ihsan Erden","doi":"10.1111/cbdd.14328","DOIUrl":"10.1111/cbdd.14328","url":null,"abstract":"<p>A series of novel 1,2,3,4-tetrazines were designed and synthesized. <sup>1</sup>H-NMR spectroscopy, <sup>13</sup>C NMR spectroscopy, and HRMS were used to determine the structures of this novel compounds. Computational approaches suggested that DHFR is a putative target for the newly synthesized 11 compounds. Extensive molecular dynamics simulations followed by molecular docking simulations were employed to evaluate DHFR as a potential target protein. The anticancer activities of the compounds were evaluated against five different types of leukemia cell lines (Jurkat, Nalm-6, Reh, K562, and Molt-4) and one non-leukemic cell line (Hek293T) by MTT test in vitro and imatinib was used as a control drug. Among these compounds, <b>3a</b> exhibited the best activity against all the leukemic cell lines, except Reh cell line. For Nalm-6, K562, Jurkat, and Molt-4 cell lines, IC<sub>50</sub> values were found to be 15.98, 19.12, 23.15, and 25.80 μM, respectively. Our work focuses on the synthesis of original and novel 1,2,3,4-tetrazine derivatives while contributing to the ongoing effort to discover more potent new antileukemia agents.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41180706","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
A review of recent advancements in Actinium-225 labeled compounds and biomolecules for therapeutic purposes 用于治疗目的的锕-225标记化合物和生物分子的最新进展综述。
Chemical biology & drug design Pub Date : 2023-09-15 DOI: 10.1111/cbdd.14311
Maria Hassan, Tanveer Hussain Bokhari, Nadeem Ahmed Lodhi, Muhammad Kaleem Khosa, Muhammad Usman
{"title":"A review of recent advancements in Actinium-225 labeled compounds and biomolecules for therapeutic purposes","authors":"Maria Hassan,&nbsp;Tanveer Hussain Bokhari,&nbsp;Nadeem Ahmed Lodhi,&nbsp;Muhammad Kaleem Khosa,&nbsp;Muhammad Usman","doi":"10.1111/cbdd.14311","DOIUrl":"10.1111/cbdd.14311","url":null,"abstract":"<p>In nuclear medicine, cancers that cannot be cured or can only be treated partially by traditional techniques like surgery or chemotherapy are killed by ionizing radiation as a form of therapeutic treatment. Actinium-225 is an alpha-emitting radionuclide that is highly encouraging as a therapeutic approach and more promising for targeted alpha therapy (TAT). Actinium-225 is the best candidate for tumor cells treatment and has physical characteristics such as high (LET) linear energy transfer (150 keV per μm), half-life (<i>t</i><sub>1/2</sub> = 9.92d), and short ranges (400–100 μm) which prevent the damage of normal healthy tissues. The introduction of various new radiopharmaceuticals and radioisotopes has significantly assisted the advancement of nuclear medicine. Ac-225 radiopharmaceuticals continuously demonstrate their potential as targeted alpha therapeutics. <sup>225</sup>Ac-labeled radiopharmaceuticals have confirmed their importance in medical and clinical areas by introducing [<sup>225</sup>Ac]Ac-PSMA-617, [<sup>225</sup>Ac]Ac-DOTATOC, [<sup>225</sup>Ac]Ac-DOTA-substance-P, reported significantly improved response in patients with prostate cancer, neuroendocrine, and glioma, respectively. The development of these radiopharmaceuticals required a suitable buffer, incubation time, optimal pH, and reaction temperature. There is a growing need to standardize quality control (QC) testing techniques such as radiochemical purity (RCP). This review aims to summarize the development of the Ac-225 labeled compounds and biomolecules. The current state of their reported resulting clinical applications is also summarized as well.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10261252","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
Resveratrol alleviates amyloid β-induced neuronal apoptosis, inflammation, and oxidative and endoplasmic reticulum stress by circ_0050263/miR-361-3p/PDE4A axis during Alzheimer's disease 在阿尔茨海默病期间,白藜芦醇通过circ_0050263/miR-361-3p/PDE4A轴减轻淀粉样蛋白β诱导的神经元凋亡、炎症以及氧化和内质网应激。
Chemical biology & drug design Pub Date : 2023-08-24 DOI: 10.1111/cbdd.14313
Yanchun Zhang, Deqiang Chen, Rui Tian, Xinyue Yan, Yingwen Zhou
{"title":"Resveratrol alleviates amyloid β-induced neuronal apoptosis, inflammation, and oxidative and endoplasmic reticulum stress by circ_0050263/miR-361-3p/PDE4A axis during Alzheimer's disease","authors":"Yanchun Zhang,&nbsp;Deqiang Chen,&nbsp;Rui Tian,&nbsp;Xinyue Yan,&nbsp;Yingwen Zhou","doi":"10.1111/cbdd.14313","DOIUrl":"10.1111/cbdd.14313","url":null,"abstract":"<p>Resveratrol (Res) has been identified to reduce neurodegeneration. Circular RNAs (circRNAs) are stable noncoding RNAs that are considered to be ideal biomarkers for molecular targeting treatment. Here, this study focused on investigating the function and relationship of circ_0050263 and Res in Alzheimer's Disease (AD). Human neuroblastoma cell line SK-N-SH was exposed to amyloid-β (Aβ) to induce AD cell model in vitro. Cell viability, apoptosis, and inflammatory reaction were evaluated by CCK-8 assay, flow cytometery, and ELISA analysis. The oxidative stress and endoplasmic reticulum stress (ERS) were determined by detecting related markers. Levels of genes and proteins were detected by qRT-PCR and Western blot. Dual-luciferase reporter assay was adopted to verify the binding between miR-361-3p and circ_0050263 or PDE4A (Phosphodiesterase 4A). Subsequently, we found that Res treatment alleviated Aβ-induced apoptosis, inflammatory response, oxidative stress, and ERS in SK-N-SH cells. Circ_0050263 is a stable circRNA, which was increased by Aβ, but decreased by Res in SK-N-SH cells. Circ_0050263 overexpression reversed Res-induced neuroprotective effects. Mechanistically, circ_0050263 acted as a sponge for miR-361-3p, which targeted PDE4A. Circ_0050263 silencing abated Aβ-induced neuronal injury, which were counteracted by following PDE4A overexpression. Moreover, PDE4A upregulation could attenuate Res-mediated neuroprotective effects. In all, Res alleviated Aβ-induced neuronal apoptosis, inflammation, oxidative stress, and ERS via circ_0050263/miR-361-3p/PDE4A axis, providing new insights for AD therapy.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067200","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
N-methylpiperazinyl and piperdinylalkyl-O-chalcone derivatives as potential polyfunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation N-甲基哌嗪基和哌啶烷基-O-查尔酮衍生物作为潜在的抗阿尔茨海默病多功能药物:设计、合成和生物学评价。
Chemical biology & drug design Pub Date : 2023-08-20 DOI: 10.1111/cbdd.14318
Pratibha Sharma, Varinder Singh, Manjinder Singh
{"title":"N-methylpiperazinyl and piperdinylalkyl-O-chalcone derivatives as potential polyfunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation","authors":"Pratibha Sharma,&nbsp;Varinder Singh,&nbsp;Manjinder Singh","doi":"10.1111/cbdd.14318","DOIUrl":"10.1111/cbdd.14318","url":null,"abstract":"<p>The series of <i>N</i>-methylpiperazinyl and piperdinylalkyl-<i>O</i>-chalcone derivatives as potential polyfuctional agents against Alzheimer's disease that have been designed, synthesized and then evaluated biologically using in vitro assays for the inhibition of acetylcholinesterase (AChE) activity, AGEs, and free radical formation. The majority of synthesized compounds inhibited AChE &amp; AGEs with additional free radical scavenging activities at nanomolar concentrations. Among these, compound <b>5k</b> was found to have potent AChE inhibitory activity (IC<sub>50</sub> = 11.6 nM), superior than the reference compound donepezil (15.68 nM) along with the good anti-AGEs and free radical formation effect. Its potency was justified by docking studies that revealed its dual binding characteristic with both catalytic active site and peripheral anionic site of AChE, simultaneously. Furthermore, the in vivo evaluation of <b>5k</b> against streptozotocin (STZ)-induced dementia in rats also showed improvement of memory functions (Morris water maze test) in animals. Also, <b>5k</b> inhibited STZ-inudced brain AChE activity and oxidative stress which further strengthen the observed in vitro effects. The stability of the ligand-protein complex was then analyzed using a simulation-based interaction protocol. The results revealed that these <i>N</i>-methylpiperazinyl and piperdinylalkyl-<i>O</i>-chalcone derivatives could be considered for potential polyfunctional anti-Alzheimer's molecules.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10031070","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
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,&nbsp;Xu Sun,&nbsp;Limin Sang,&nbsp;Min Zhang,&nbsp;Xubo Yan,&nbsp;Qi Ju,&nbsp;Xuefeng Ma,&nbsp;Meng Xu","doi":"10.1111/cbdd.14330","DOIUrl":"10.1111/cbdd.14330","url":null,"abstract":"<p>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.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":null,"pages":null},"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,&nbsp;Ding Sun,&nbsp;Lu Zou,&nbsp;Shaobin Li,&nbsp;Ling Tang,&nbsp;Xiao Yu,&nbsp;Binqing Tang,&nbsp;Yingen Wu,&nbsp;Hong Fang","doi":"10.1111/cbdd.14302","DOIUrl":"10.1111/cbdd.14302","url":null,"abstract":"<p>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.</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":null,"pages":null},"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,&nbsp;Abdullah Mohammed Al-Majid,&nbsp;Matti Haukka,&nbsp;Zahida Parveen,&nbsp;Nabeela Ravaiz,&nbsp;Abdul Wadood,&nbsp;Ashfaq Ur Rehman,&nbsp;Mar Ríos-Gutiérrez,&nbsp;Luis R. Domingo,&nbsp;Assem Barakat","doi":"10.1111/cbdd.14299","DOIUrl":"10.1111/cbdd.14299","url":null,"abstract":"<p>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 <b>6</b> has also been studied with Molecular Electron Density Theory. The high nucleophilic character of AY 10, <i>N</i> = 4.39 eV, allows explaining that the most favorable <b>TS-on</b> is 13.9 kcal mol<sup>−1</sup> below the separated reagent. This 32CA, which takes place through a non-concerted one-step mechanism, presents a total <i>ortho</i> regio- and <i>endo</i> stereoselectivity, which is controlled by the formation of two intramolecular H<sup>…</sup>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).</p>","PeriodicalId":93931,"journal":{"name":"Chemical biology & drug design","volume":null,"pages":null},"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
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