{"title":"Comment on “Integrative Analysis of Ex Vivo Studies and Microarray Reveals the Novel Inhibitor Effects of Trehalose on the Pathogenesis of Pterygium”","authors":"Thiago Gonçalves dos Santos Martins","doi":"10.1111/cbdd.14636","DOIUrl":"10.1111/cbdd.14636","url":null,"abstract":"","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334360","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, Antioxidant Activity, and Molecular Docking of Novel Paeoniflorin Derivatives","authors":"Jiating Ni, Meng Yang, Xinyue Zheng, Mingtao Wang, Qian Xiao, Hua Han, Peiliang Dong","doi":"10.1111/cbdd.14629","DOIUrl":"https://doi.org/10.1111/cbdd.14629","url":null,"abstract":"<div>\u0000 \u0000 <p>Paeoniflorin (PF) is one of the active constituents of the traditional Chinese medicine <i>Paeoniae Radix</i> Rubra and has been actively explored in the pharmaceutical area due to its numerous pharmacological effects. However, severe difficulties such as limited bioavailability and low permeability limit its utilization. Therefore, this study developed and synthesized 25 derivatives of PF, characterized them by <sup>1</sup>H NMR, <sup>13</sup>C NMR, and HR-MS, and evaluated their antioxidant activity. Firstly, the antioxidant capacity of PF derivatives was investigated through DPPH radical scavenging experiment, ABTS radical scavenging experiment, reducing ability experiment, and O<sub>2</sub><sup>.−</sup> radical scavenging experiment. PC12 cells are routinely used to evaluate the antioxidant activity of medicines, therefore we utilize it to establish a cellular model of oxidative stress. Among all derivatives, compound 22 demonstrates high DPPH radical scavenging capacity, ABTS radical scavenging ability, reduction ability, and O<sub>2</sub><sup>.−</sup> radical scavenging ability. The results of cell tests reveal that compound 22 has a non-toxic effect on PC12 cells and a protective effect on H<sub>2</sub>O<sub>2</sub>-induced oxidative stress models. This might be due to the introduction of 2, 5-difluorobenzene sulfonate group in PF, which helps in scavenging free radicals under oxidative stress. Western blot and molecular docking indicated that compound 22 may exert antioxidant activity by activating Nrf2 protein expression. As noted in the study, compound 22 has the potential to be a novel antioxidant.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324674","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":"Dehydroepiandrosterone-α-2-Deoxyglucoside Exhibits Enhanced Anticancer Effects in MCF-7 Breast Cancer Cells and Inhibits Glucose-6-Phosphate Dehydrogenase Activity","authors":"Hsu-Feng Liu, Shen-Chieh Chou, Sheng-Cih Huang, Tzu-Yu Huang, Po-Yun Hsiao, Feng-Pai Chou, Tung-Kung Wu","doi":"10.1111/cbdd.14624","DOIUrl":"https://doi.org/10.1111/cbdd.14624","url":null,"abstract":"<p>In the pentose phosphate pathway, dehydroepiandrosterone (DHEA) uncompetitively inhibits glucose-6-phosphate dehydrogenase (G6PD), reducing NADPH production and increasing oxidative stress, which can influence the onset and/or progression of several diseases, including cancer. 2-Deoxy-D-glucose (2-DG), a glucose mimetic, competes with glucose for cellular uptake, inhibiting glycolysis and competing with glucose-6-phosphate (G-6-P) for G6PD activity. In this study, we report that DHEA-α-2-DG (<b>5</b>), an α-covalent conjugate of DHEA and 2-DG, exhibits better anticancer activity than DHEA, 2-DG, DHEA +2-DG, and polydatin in MCF-7 cells, and reduces NADPH/NADP<sup>+</sup> ratio in cellular assays. In vitro enzyme kinetics and molecular docking studies showed that <b>5</b> uncompetitively inhibits human G6PD activity and binds to the structural NADP<sup>+</sup> site but not to the catalytic NADP<sup>+</sup> site. Further combining <b>5</b> with the FDA-approved drug tamoxifen enhanced its cytotoxicity against MCF-7 cells, suggesting that it could serve as a candidate for combination of drug strategies.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.14624","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aamir Mehmood, Mohd Sajid Ali, Daixi Li, Aman Chandra Kaushik, Dong-Qing Wei
{"title":"Unveiling the Therapeutic Potential of Paclitaxel Combinations Against Breast Carcinoma and Identification of In Vivo Biomarkers","authors":"Aamir Mehmood, Mohd Sajid Ali, Daixi Li, Aman Chandra Kaushik, Dong-Qing Wei","doi":"10.1111/cbdd.14627","DOIUrl":"https://doi.org/10.1111/cbdd.14627","url":null,"abstract":"<div>\u0000 \u0000 <p>Breast cancer (BC) is one of the leading causes of high mortality rates in women worldwide. Although advancements have been made in the design of therapeutic strategies and drug discovery, drug resistance remains one of the key challenges. One of the ways to overcome drug resistance is finding potential drug combinations since the efficacy of combined drugs is higher than their individual efficacies if the combination is a synergistic pair. Therefore, the current study uses a BC patient-derived xenograft (PDX) dataset to evaluate the effects of various cancer drugs on breast cancer in vivo models. The drug effects are further validated by four machine learning models, namely Elastic Net, Least Absolute Shrinkage and Selection (LASSO), Support Vector Machine (SVM), Random Forests (RF), as well as exploring the shortlisted drugs in combination with paclitaxel, a baseline drug for enhanced efficacy on tumor volume reduction. Additionally, the study also shortlists the top 50 in vivo biomarkers correlated with the effects of the drugs. The outcomes could be significantly important for the design of an effective anti-breast cancer therapy.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316892","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":"One-Step Organic Synthesis of 18β-Glycyrrhetinic Acid-Anthraquinone Ester Products: Exploration of Antibacterial Activity and Structure–Activity Relationship, Toxicity Evaluation in Zebrafish","authors":"Zhaoyi Yang, Xueyan Li, Wei Liu, Guangyue Wang, Jiahui Ma, Lulu Jiang, Denghui Yu, Yuling Ding, Yong Li","doi":"10.1111/cbdd.14631","DOIUrl":"https://doi.org/10.1111/cbdd.14631","url":null,"abstract":"<div>\u0000 \u0000 <p>To combine the activity characteristics of 18<i>β</i>-glycyrrhetinic acid (18<i>β</i>-GA) and anthraquinone compounds (rhein and emodin), reduce toxicity, and explore the structure–activity relationship (SAR) of anthraquinones, 18<i>β</i>-GA-anthraquinone ester compounds were synthesized by one-step organic synthesis. The products were separated and purified by HPLC and characterized by NMR and EI-MS. It was finally determined as di-18<i>β</i>-GA-3-rhein ester (<b>1</b>, New), GA dimer (<b>2</b>, known), 18<i>β</i>-GA-3-emodin ester (<b>3</b>, known), and di-18<i>β</i>-GA-1-emodin ester (<b>4</b>, new). The MIC of three reactants and four products against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> were detected in vitro. Its developmental toxicity and cardiotoxicity were assessed using zebrafish embryos. The experimental results showed that rhein had the best antibacterial activity against <i>Staphylococcus aureus</i> with MIC<sub>50</sub> of 2.4 mM, and it was speculated that –COOH, –OH, and intramolecular hydrogen bonds in anthraquinone compounds would enhance the antibacterial effect, while the presence of-CH<sub>3</sub> might weaken the antibacterial activity. Product <b>1</b> increased the hatching rate and survival rate of zebrafish embryos and reduced the malformation rate and cardiomyocyte apoptosis. This experiment lays the foundation for further studying the SAR of anthraquinones and providing new drug candidates.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316894","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":"Myrtenol-Loaded Fatty Acid Nanocarriers Protect Rat Brains Against Ischemia–Reperfusion Injury: Antioxidant and Anti-Inflammatory Effects","authors":"Shima Karimi Afshar, Farzaneh Rostamzadeh, Mohammad Reza Bigdeli, Fatemeh Mortazavi Moghadam","doi":"10.1111/cbdd.14633","DOIUrl":"https://doi.org/10.1111/cbdd.14633","url":null,"abstract":"<div>\u0000 \u0000 <p>This research investigated the preventive effects of myrtenol (MYR), fatty acid nanocarriers (FANC), and myrtenol-loaded FANC (MYR + FANC) on neurological disturbance, stroke volume, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and tumor necrosis factor-alpha (TNF-α) in the brain with ischemia<b>–</b>reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in rats. Seventy two Wistar male rats were divided into six main groups. The groups were sham, ischemia<b>–</b>reperfusion group (MACO), MACO-MYR (50 mg/kg), MACO-FANC (50 and 100 mg/kg), and MACO-MYR + FANC (50 mg/kg). Stroke volume, neurological deficit scores, and the brain levels of MDA, SOD, and TNF-α were examined with TTC staining, observation, and ELISA, respectively. Pretreatment with MYR, FANC (100 mg/kg), and MYR + FANC reduced the neurological deficit score and cerebral infarction volume. MYR, FANC (100 mg/kg), and MYR + FANC pretreatment increased and decreased brain SOD and MDA levels compared to MACO group, respectively. The TNF-α level decreased in the MYR + FANC group compared to MCAO and MCAO-MYR groups in the brain. The use of FANC (100 mg/kg), MYR, and MYR + FANC has protective effects against oxidative stress and ischemia<b>–</b>reperfusion injury. FANC probably improve the bioavailability of MYR, as MYR+ FANC had more therapeutic effects on the reduction of ischemia–reperfusion injuries, inflammation, and oxidative stress.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316890","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":"Thymol and p-Cymene Protect the Liver by Mitigating Oxidative Stress, Suppressing TNF-α/NF-κB, and Enhancing Nrf2/HO-1 Expression in Immobilized Rats","authors":"Yasaman Peirovy, Masoumeh Asle-Rousta","doi":"10.1111/cbdd.14618","DOIUrl":"10.1111/cbdd.14618","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to investigate the effects of the monoterpenes thymol and p-cymene on the liver of rats subjected to prolonged immobilization stress and to discover the possible mechanism behind this effect. For 14 consecutive days, the rats were placed in a restrainer for 2.5 h every day to expose them to stress. During the same period, thymol (10 mg/kg, gavage) and p-cymene (50 mg/kg, intraperitoneally) were also administered. Thymol and p-cymene prevented the increase in malondialdehyde levels and the decrease in glutathione content in the liver of rats exposed to chronic immobility. They also increased the activity of the glutathione peroxidase enzyme in the liver of stressed animals, but only thymol could increase the activity of superoxide dismutase. These monoterpenes reduced the expression of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 and nuclear factor kappa B (NF-κB) in the liver of stressed animals. They increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Thymol and p-cymene greatly prevented the infiltration of inflammatory cells in the liver parenchyma of stressed rats. In conclusion, the study found that thymol and p-cymene have a hepatoprotective effect on immobilized rats, likely exerted by suppressing oxidative stress and inflammation, stimulating Nrf2/HO-1 signaling, and inhibiting the TNF-α/NF-κB pathway.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309364","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}
Yawen Chen, Hongshun Gu, Danni Ye, Yi Li, Yan Chen, Haoyi Qiao, Yujiao Huang, Ran Tao, Shuhui Yu, Jianjun Zhang, Wenting Fei, Linyuan Wang
{"title":"NMC-4 Ameliorates Depression-Like Behavior and Neuroinflammation Caused by Chronic Unpredictable Mild Stress","authors":"Yawen Chen, Hongshun Gu, Danni Ye, Yi Li, Yan Chen, Haoyi Qiao, Yujiao Huang, Ran Tao, Shuhui Yu, Jianjun Zhang, Wenting Fei, Linyuan Wang","doi":"10.1111/cbdd.14626","DOIUrl":"https://doi.org/10.1111/cbdd.14626","url":null,"abstract":"<p>Depression is a prevalent mental disorder, but the side effects of antidepressants also make depressed patients resistant. Effective and safe antidepressants should be developed from traditional herbs, with the aim of reducing the side effects of antidepressants and improving the efficacy of drugs. In this study, the new macamide compound-4 (NMC-4) was synthesized for the first time, addressing the problem of difficult extraction, isolation, and low content of natural macamide. NMC-4 was characterized using mass spectrometry, nuclear magnetic resonance, and infrared spectroscopy. The protective effect of NMC-4 against cell injury was demonstrated to be stronger than that of natural macamide (<i>N</i>-benzylhexadecanamide, XA) using a PC12 cell injury model. The study explored the effects of NMC-4 on chronic unpredictable mild stress (CUMS)-induced depressive symptoms. NMC-4 significantly improved depressive-like behaviors. NMC-4 ameliorated CUMS-induced depressive-like behaviors by mitigating neuroinflammation and modulating the NF-κB/Nrf2 and BDNF/PI3K/Akt pathways.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.14626","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New Cytotoxic α-Aminoacylamide and bis-1,5-Disubstituted Tetrazole Adducts From Amino-Diterpene Molecules by Ugi Reaction","authors":"Anna Smirnova, Elena Tretyakova, Oxana Kazakova","doi":"10.1111/cbdd.14632","DOIUrl":"https://doi.org/10.1111/cbdd.14632","url":null,"abstract":"<div>\u0000 \u0000 <p>In search for new molecules of diterpene origin with promising anticancer activity, two amino-derivatives (methyl maleopimarate aminoimide and methyl 1β,13-epoxydihydroquinopimarate C4-hydrazone) were involved in the 4-component Ugi reaction (Ugi-4CR) and pseudo-7-component azido-Ugi condensation (azido-Ugi-7CR) to afford a series of adducts holding α-aminoacylamide and <i>bis</i>-1,5-disubstituted tetrazole substituents. The NCI-60 cancer cell panel screening revealed diterpene-type Ugi adducts <b>2</b>, <b>5</b>, and <b>6</b> with strong antiproliferative potency with GI<sub>50</sub> in range of 1.2–15.4 μM. The high positive correlations with standard anticancer drugs suggest microtubules or progesterone and androgen receptors as possible targets of the synthesized compounds.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276589","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}
Nurul Alam Inayatsyah, Mohamad Jemain Mohamad Ridhwan, Alim Alsukor Aznirulhisham, Nurulfazlina Edayah Rasol, Noraini Kasim, Syahrul Imran
{"title":"Synthesis of Novel Soritin Sulfonamide Derivatives as Potential α-Glucosidase Inhibitor and Their Molecular Docking Studies","authors":"Nurul Alam Inayatsyah, Mohamad Jemain Mohamad Ridhwan, Alim Alsukor Aznirulhisham, Nurulfazlina Edayah Rasol, Noraini Kasim, Syahrul Imran","doi":"10.1111/cbdd.14614","DOIUrl":"10.1111/cbdd.14614","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetes Mellitus (DM) is linked to various factors causing cardiovascular diseases, with uncontrolled postprandial hyperglycemia being a direct contributor. <i>α</i>-Glucosidase inhibitors (AGIs) aid in reducing postprandial hyperglycemia, potentially mitigating cardiovascular risks. In order to synthesize novel chemical scaffolds with possible <i>α-</i>glucosidase inhibition activity, a series of novel soritin sulfonamide derivatives were synthesized. The soritin hydrazide was treated with various aryl sulfonyl chlorides to obtain targeted compounds (<b>1–16</b>). Findings suggested that all compounds have better <i>α-</i>glucosidase inhibition compared to standard drugs, acarbose (2187.00 ± 1.25 μM) and 1-deoxynojirimycin (334.90 ± 1.10 μM), with IC<sub>50</sub> values ranging from 3.81 ± 1.67 μM to 265.40 ± 1.58 μM. The most potent analog was Compound <b>13</b>, a trichloro phenyl substituted compound, with IC<sub>50</sub> value of 3.81 ± 1.67 μM. Structure–activity relationship (SAR) showed that introducing an additional chlorine group into the parent nucleus increases the potency. The docking studies validated that Compound <b>13</b> established hydrogen bonds with the active site residues Asp214, Glu276, and Asp349, while being further stabilized by hydrophobic interactions, providing an explanation for its high potency.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269856","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}