Chemical Biology & Drug Design最新文献

A Comprehensive Analysis on Galantamine Based Hybrids for the Management of Alzheimer's Disease 全面分析基于加兰他敏的混合药物对阿尔茨海默病的治疗作用。

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2024-11-04 DOI: 10.1111/cbdd.70004

Yash Pal Singh, Sonima Prasad, Harish Kumar

{"title":"A Comprehensive Analysis on Galantamine Based Hybrids for the Management of Alzheimer's Disease","authors":"Yash Pal Singh, Sonima Prasad, Harish Kumar","doi":"10.1111/cbdd.70004","DOIUrl":"10.1111/cbdd.70004","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) is a progressive chronic age-related neurodegenerative brain disorder characterized by the loss of memory and other cognitive functions. The exact etiology of AD is still under investigation, however several factors such as low level of neurotransmitter acetylcholine (ACh), aggregation of amyloid beta (Aβ) in the form of Aβ plaques, hyperphosphorylation of tau protein into neurofibrillary tangles (NFTs), oxidative stress, and metal ion imbalance are the major hallmarks of this disease. Of the multiple hypotheses for AD, the amyloid-β (Aβ) and cholinergic hypothesis are the main targeting hypotheses for AD. Some researchers hypothesized that the primary event associated with the cholinergic neurotransmitter (acetylcholine) is memory loss and cognitive impairment. Due to the disease's complicated pathogenesis, long-term therapy with a single target candidate is futile. As a result, multitargeted and multifunctional therapies have emerged. Various research teams are concentrating on addressing multiple disease factors through hybridization techniques. Consequently, this hybridization approach has been applied to all core scaffolds, including galantamine. In this article, we tried to provide a thorough overview of the most recent developments on galantamine, a prospective AChE inhibitor, and its hybrid analogs as possible therapeutic agents for treating AD. Furthermore, we also provided the design, synthesis, and SAR analysis of the galantamine-based compounds used in the last decades for the management of AD.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570587","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}

引用次数: 0

CRBN-PROTACs in Cancer Therapy: From Mechanistic Insights to Clinical Applications CRBN-PROTACs 在癌症治疗中的应用：从机理认识到临床应用。

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2024-11-04 DOI: 10.1111/cbdd.70009

Riya Thapa, Asif Ahmad Bhat, Gaurav Gupta, S. Renuka Jyothi, Irwanjot Kaur, Sachin Kumar, Naveen Sharma, G. V. Siva Prasad, Atreyi Pramanik, Haider Ali

{"title":"CRBN-PROTACs in Cancer Therapy: From Mechanistic Insights to Clinical Applications","authors":"Riya Thapa, Asif Ahmad Bhat, Gaurav Gupta, S. Renuka Jyothi, Irwanjot Kaur, Sachin Kumar, Naveen Sharma, G. V. Siva Prasad, Atreyi Pramanik, Haider Ali","doi":"10.1111/cbdd.70009","DOIUrl":"10.1111/cbdd.70009","url":null,"abstract":"<div>\u0000 \u0000 <p>Cereblon (CRBN), a member of the E3 ubiquitin ligase complex, has gained significant attention as a therapeutic target in cancer. CRBN regulates the degradation of various proteins in cancer progression, including transcription factors and signaling molecules. PROTACs (proteolysis-targeting chimeras) are a novel approach that uses the cell's degradation system to remove disease-causing proteins selectively. CRBN-dependent PROTACs work by tagging harmful proteins for destruction through the ubiquitin–proteasome system. This strategy offers several advantages over traditional protein inhibition methods, including the potential to overcome drug resistance. Recent progress in developing CRBN-based PROTACs has shown promising preclinical results in both hematologic malignancies and solid tumors. Additionally, CRBN-based PROTACs have enhanced our understanding of CRBN's role in cancer, potentially serving as biomarkers for patient stratification and predicting therapeutic responses. In this review, we delineate the mechanisms of action for CRBN-dependent PROTACs (CRBN-PROTACs), summarize recent advances in preclinical and clinical applications, and provide our perspective on future development.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577188","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}

引用次数: 0

In Vitro Cytotoxicity and Mechanistic Investigation of Quinazolin-4(1H)-One Linked Coumarin as a Potent Anticancer Agent 喹唑啉-4(1H)-单链香豆素作为强效抗癌剂的体外细胞毒性和机理研究

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2024-11-04 DOI: 10.1111/cbdd.70011

Dinesh Singla, Palak Sharma, Vijay Luxami, Kamaldeep Paul

{"title":"In Vitro Cytotoxicity and Mechanistic Investigation of Quinazolin-4(1H)-One Linked Coumarin as a Potent Anticancer Agent","authors":"Dinesh Singla, Palak Sharma, Vijay Luxami, Kamaldeep Paul","doi":"10.1111/cbdd.70011","DOIUrl":"10.1111/cbdd.70011","url":null,"abstract":"<div>\u0000 \u0000 <p>Quinazolinone-coumarin conjugates synthesized through Late-Stage Functionalization approach are evaluated for their in vitro biological activity for 60 human cancer cell lines representing nine different cancer types. Among the synthesized compounds, eight displayed significant growth inhibitory activity across a spectrum of cancer types, with compound <b>23</b> demonstrating particularly notable cytotoxicity. Further investigation involved a five-dose assay of compound <b>23</b> against NCI-60 cancer cell lines, revealing its efficacy at different concentrations. Additionally, binding studies elucidated its interaction with Human Serum Albumin (HSA) and DNA. The results indicated a strong binding affinity of <b>23</b> with HSA, evidenced by a high binding constant (2.26 × 10<sup>5</sup> M<sup>−1</sup>). Moreover, its interaction with DNA occurred via intercalation, specifically between the base pairs of DNA strands, with a binding constant of 5.51 × 10<sup>4</sup> M<sup>−1</sup>. This suggests that compound <b>23</b> has the ability to bind to both DNA and transport proteins, making it a promising pharmacophore with potential therapeutic applications.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577189","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}

引用次数: 0

Mitotic Arrest Deficient 2 Like 1 Contributes to Colorectal Cancer Cell Migration, Invasion, and Oxaliplatin Resistance Through the Wnt/β-Catenin Pathway 有丝分裂停滞缺陷 2 Like 1 通过 Wnt/β-Catenin 通路促进结直肠癌细胞迁移、侵袭和奥沙利铂耐药性的形成

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2024-11-01 DOI: 10.1111/cbdd.70012

Xiang Ding, Yonggui Zhou, Linfang He, Hubin Kang, Youwu Wen, Jia Xu, Congbo Zhu, Libing Luo, Qingjun Zeng

{"title":"Mitotic Arrest Deficient 2 Like 1 Contributes to Colorectal Cancer Cell Migration, Invasion, and Oxaliplatin Resistance Through the Wnt/β-Catenin Pathway","authors":"Xiang Ding, Yonggui Zhou, Linfang He, Hubin Kang, Youwu Wen, Jia Xu, Congbo Zhu, Libing Luo, Qingjun Zeng","doi":"10.1111/cbdd.70012","DOIUrl":"10.1111/cbdd.70012","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) is a highly prevalent malignancy, requiring chemotherapy for advanced stages of the disease. Previously, we found that mitotic arrest deficient 2 like 1 (MAD2L1) was upregulated and facilitated malignant proliferation in CRC. However, the association between MAD2L1 expression and tumor progression, as well as chemotherapy resistance in CRC, remains unclear. The progression capacities of CRC cells were assessed using transwell and wound healing assays, and the resistance to cisplatin in oxaliplatin-resistant CRC cells was assessed using CCK-8 assay and flow cytometry. Relevant protein levels of epithelial-to-mesenchymal transition (EMT) and Wnt/β-catenin pathway were analyzed using western blotting. Revealing the impact of MAD2L1 on metastasis and drug resistance in CRC through inhibition of the Wnt/β-catenin pathway. Knockdown of MAD2L1 attenuated the malignant progression of CRC cells, inhibited EMT, and blocked the Wnt/β-catenin pathway. MAD2L1 was significantly upregulated in oxaliplatin-resistant CRC cells, accompanied by the activation of the Wnt/β-catenin pathway. Knockdown of MAD2L1 effectively reversed oxaliplatin resistance, leading to apoptosis and downregulation of the protein expression levels of β-catenin, P-glycoprotein (P-gp), and ABCG2. After the knockdown of MAD2L1, the inhibition of the Wnt/β-catenin pathway exhibited a synergistic effect, effectively suppressing malignant progression and reversing oxaliplatin resistance in CRC cells. So, knockdown of MAD2L1 suppressed cell malignant progression, equally sensitized resistant CRC cells to oxaliplatin, potentially by blocking the activation of the Wnt/β-catenin pathway.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565317","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}

引用次数: 0

Comprehensive Analysis of NADH:Ubiquinone Oxidoreductase Subunit B3 in Gynecological Tumors and Identification of Its Natural Inhibitor Wedelolactone 妇科肿瘤中 NADH:Ubiquinone 氧化还原酶亚基 B3 的全面分析及其天然抑制剂蟛蜞菊内酯的鉴定

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2024-10-29 DOI: 10.1111/cbdd.70006

Huiping Li, Yangli Jin, Yanyan Zhang, Xiaohua Xie, Nan Li

{"title":"Comprehensive Analysis of NADH:Ubiquinone Oxidoreductase Subunit B3 in Gynecological Tumors and Identification of Its Natural Inhibitor Wedelolactone","authors":"Huiping Li, Yangli Jin, Yanyan Zhang, Xiaohua Xie, Nan Li","doi":"10.1111/cbdd.70006","DOIUrl":"10.1111/cbdd.70006","url":null,"abstract":"<div>\u0000 \u0000 <p>The aim of this study was to explore the role of NADH:ubiquinone oxidoreductase subunit B3 (NDUFB3) in human gynecological malignancies and to screen potential natural compounds targeting it. GEPIA and HPA databases were used to study the expression characteristics of NDUFB3. GO and KEGG enrichment analyses were performed using the R software clusterProfiler package. GSEA for NDUFB3 was performed using the LinkedOmics database. Natural compounds targeting NDUFB3 were screened by virtual screening and molecular docking. After NDUFB3 was depleted or wedelolactone treatment, cell proliferation was detected by CCK-8 assay. The production of reactive oxide species (ROS) in tumor cells was detected by dihydroethidium fluorescent probe. The cell cycle and apoptosis were evaluated by flow cytometry. It was revealed that NDUFB3 was highly expressed in ovarian cancer (OV), uterine corpus endometrial carcinoma (UCEC), and cervical squamous cell carcinoma (CESC). NDUFB3 expression was associated with multiple immunomodulators in CESC, OV, and UCEC. NDUFB3 was predicted to modulate MAPK signaling pathways in CESC, OV, and UCEC. Knocking down NDUFB3 inhibited the proliferation of CESC, OV, and UCEC cells, increased intracellular ROS production, and induced cell cycle arrest and apoptosis. Wedelolactone was a potential small molecule with a strong ability to bind with the active pocket of NDUFB3, and wedelolactone could kill CESC, OV, and UCEC cells partly via NDUFB3. In conclusion, NDUFB3 may be a potential biomarker and a new target for gynecological tumors, and wedelolactone may exert antitumor activity via targeting NDUFB3.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523841","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}

引用次数: 0

Design and Synthesis of 1,4-Diformyl-Piperazine Ferrostatin-1 Derivatives as Novel Ferroptosis Inhibitors 1,4-Diformyl-Piperazine Ferrostatin-1 衍生物作为新型铁氧化酶抑制剂的设计与合成。

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2024-10-28 DOI: 10.1111/cbdd.70000

Yi-Fan Zhang, Wei Guo, Hui Zheng, Nai-Yu Zhang, Hua-Long Ji, Ning Meng, Juan Zhang, Cheng-Shi Jiang

引用次数: 0

Combination of Diosmetin With Chrysin Against Hepatocellular Carcinoma Through Inhibiting PI3K/AKT/mTOR/NF-кB Signaling Pathway: TCGA Analysis, Molecular Docking, Molecular Dynamics, In Vitro Experiment Diosmetin 与 Chrysin 通过抑制 PI3K/AKT/mTOR/NF-кB 信号通路联合对抗肝细胞癌：TCGA 分析、分子对接、分子动力学、体外实验。

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2024-10-24 DOI: 10.1111/cbdd.70003

Xiang Yu, Di Zhang, Chengming Hu, Zejun Yu, Yang Li, Cheng Fang, Yinsheng Qiu, Zhinan Mei, Lingyun Xu

{"title":"Combination of Diosmetin With Chrysin Against Hepatocellular Carcinoma Through Inhibiting PI3K/AKT/mTOR/NF-кB Signaling Pathway: TCGA Analysis, Molecular Docking, Molecular Dynamics, In Vitro Experiment","authors":"Xiang Yu, Di Zhang, Chengming Hu, Zejun Yu, Yang Li, Cheng Fang, Yinsheng Qiu, Zhinan Mei, Lingyun Xu","doi":"10.1111/cbdd.70003","DOIUrl":"10.1111/cbdd.70003","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is the sixth most prevalent malignant tumor. Hepatocellular carcinogenesis is closely linked to apoptosis, autophagy, and inflammation. Diosmetin and chrysin, are two flavonoid compounds, exhibit anti-inflammatory and anticancer properties. In this study, the TCGA database was utilized to identify differentially expressed genes between normal subjects and HCC patients. Molecular docking and molecular dynamics analyses were employed to assess the binding affinity of chrysin and diosmetin to key proteins in the PI3K/AKT/mTOR/NF-κB signaling pathway. Western blotting and RT-qPCR were used to measure the protein and gene expression within this pathway. The results indicated that HCC patients had elevated levels of PI3K, AKT, mTOR, and P65 proteins compared to normal subjects, which adversely affected patient survival. Molecular docking and dynamics studies demonstrated that diosmetin and chrysin are effectively bound to these four proteins. In vitro experiments revealed that the combination of diosmetin and chrysin could induce apoptosis, enhance autophagy, reduce inflammatory mediator production, and improve the tumor cell microenvironment by inhibiting the PI3K/AKT/mTOR/NF-κB signaling pathway. Notably, the synergy score for the combination of diosmetin (25 μM) and chrysin (10 μM) was 16. Thus, the diosmetin–chrysin combination shows promise as an effective therapeutic approach for hepatocellular carcinoma due to its strong synergistic effect.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514624","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}

引用次数: 0

Identification of BAY61-3606 Derivatives With Improved Activity in Splicing Modulation That Induces Inclusion of Cassette Exons Similar to the Splicing Factor 3B Subunit 1 Mutation 鉴定 BAY61-3606 衍生物，该衍生物在剪接调节中具有更强的活性，可诱导与剪接因子 3B 亚基 1 突变相似的盒式外显子的包含。

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2024-10-22 DOI: 10.1111/cbdd.70002

Takanori Matsumaru, Toshiki Iwamatsu, Kana Ishigami, Makoto Inai, Wataru Kanto, Ayumi Ishigaki, Atsushi Toyoda, Satoshi Shuto, Katsumi Maenaka, Shinichi Nakagawa, Hiroshi Maita

{"title":"Identification of BAY61-3606 Derivatives With Improved Activity in Splicing Modulation That Induces Inclusion of Cassette Exons Similar to the Splicing Factor 3B Subunit 1 Mutation","authors":"Takanori Matsumaru, Toshiki Iwamatsu, Kana Ishigami, Makoto Inai, Wataru Kanto, Ayumi Ishigaki, Atsushi Toyoda, Satoshi Shuto, Katsumi Maenaka, Shinichi Nakagawa, Hiroshi Maita","doi":"10.1111/cbdd.70002","DOIUrl":"10.1111/cbdd.70002","url":null,"abstract":"<div>\u0000 \u0000 <p>Splicing modulation by a small compound offers therapeutic potential for diseases caused by splicing abnormality. However, only a few classes of compounds that can modulate splicing have been identified. We previously identified BAY61-3606, a multiple kinase inhibitor, as a compound that relaxes the splicing fidelity at the 3′ splice site recognition. We have also reported the synthesis of derivatives of BAY61-3606. In this study, we tested those compounds for their splicing modulation capabilities and identified two contrasting compounds. These compounds were further investigated for their effects on the whole transcriptome, and analysis of changes in transcription and splicing revealed that the highly active derivative in the splicing reporter assay also showed significantly higher activity in modulating the splicing of endogenously expressed genes. Particularly, cassette exon inclusion was highly upregulated by this compound, and clustering analysis revealed that these effects resembled those in splicing factor 3b subunit 1 (SF3B1) K700E mutant cells but contrasted with those of the splicing inhibitor H3B-8800. Additionally, a group of serine/arginine-rich (SR) protein genes was identified as representatively affected, likely via modulation of poison exon inclusion. This finding could guide further analysis of the mode of action of these compounds on splicing, which could be valuable for developing drugs for diseases associated with splicing abnormalities.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514625","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}

引用次数: 0

Directed Design, Screening and Antiglycation Activity for 3-Substituted Thiazolium Derivatives, New Analogs of Alagebrium 3-取代噻唑鎓衍生物--阿拉吉铵的新类似物--的定向设计、筛选和抗糖化活性

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2024-10-18 DOI: 10.1111/cbdd.14630

Olga N. Zhukovskaya, Alexandra A. Kolodina, Roman Litvinov, Umida Ibragimova, Nikita Valuisky, Svetlana Sorokina, Xenia Zhukova, Diana Yu. Pobedinskaya, Alexander Borisov, Denis A. Babkov, Alexander A. Spasov

{"title":"Directed Design, Screening and Antiglycation Activity for 3-Substituted Thiazolium Derivatives, New Analogs of Alagebrium","authors":"Olga N. Zhukovskaya, Alexandra A. Kolodina, Roman Litvinov, Umida Ibragimova, Nikita Valuisky, Svetlana Sorokina, Xenia Zhukova, Diana Yu. Pobedinskaya, Alexander Borisov, Denis A. Babkov, Alexander A. Spasov","doi":"10.1111/cbdd.14630","DOIUrl":"https://doi.org/10.1111/cbdd.14630","url":null,"abstract":"<div>\u0000 \u0000 <p>Preliminary ab initio calculations led to the synthesis of novel substituted thiazolium salts, analogs of Alagebrium, which were further explored in vitro for their potential as inhibitors of the glycation reaction utilizing three distinct assays: inhibition of fluorescent AGEs formation, anticrosslinking, and deglycation. Despite the unidirectionality of the assays, distinct differences were observed in the mechanisms of interference and activity manifestation by the compounds. The gathered data permitted the formation of hypotheses about the molecular fragments of the studied antiglycators that are of utmost significance in each assay, thereby guiding future design endeavors. Potential mechanisms of actions are discussed therein. The compound 4-meth-yl-3-[2-(4-methylbiphenyl-4-yl)-2-oxoethyl] thiazolium bromide displayed high activity across all three assays, establishing it as a lead compound. The cytotoxicological properties of the compounds were evaluated using LDH and MTT assays. However, the lead compound exhibited cytotoxicity, indicating the need for additional investigations aimed at decreasing toxicity while maintaining activity. The targeted thiazolium salts were synthesized through an <i>N</i>-alkylation reaction between the corresponding thiazoles and phenacyl bromides.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448987","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}

引用次数: 0

Novel Synthesized Benzophenone Thiazole Hybrids Exhibited Ex Vivo and In Silico Anti-Inflammatory Activity 新合成的二苯甲酮噻唑杂环具有体内外抗炎活性

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2024-10-18 DOI: 10.1111/cbdd.14634

Luiz Paulo Melchior de Oliveira Leão, Albert Katchborian Neto, Karen de Jesus Nicácio, Stefânia Neiva Lavorato, Fernanda Brito Leite, Karina Camargo Teixeira, Michael Murgu, Ana Cláudia Chagas de Paula, Marisi Gomes Soares, Daniela Aparecida Chagas-Paula, Danielle Ferreira Dias

{"title":"Novel Synthesized Benzophenone Thiazole Hybrids Exhibited Ex Vivo and In Silico Anti-Inflammatory Activity","authors":"Luiz Paulo Melchior de Oliveira Leão, Albert Katchborian Neto, Karen de Jesus Nicácio, Stefânia Neiva Lavorato, Fernanda Brito Leite, Karina Camargo Teixeira, Michael Murgu, Ana Cláudia Chagas de Paula, Marisi Gomes Soares, Daniela Aparecida Chagas-Paula, Danielle Ferreira Dias","doi":"10.1111/cbdd.14634","DOIUrl":"https://doi.org/10.1111/cbdd.14634","url":null,"abstract":"<div>\u0000 \u0000 <p>Novel benzophenone–thiazole hybrids with different substituents were synthesized and evaluated for anti-inflammatory activity using an ex vivo human whole-blood assay. All hybrids (<b>3c</b> and <b>5a–h</b>) showed significant anti-inflammatory activity via prostaglandin E2 (PGE2) release inhibition. Moreover, <b>5c</b> (82.8% of PGE2 inhibition), <b>5e</b> (83.1% of PGE2 inhibition), and <b>5h</b> (82.1% of PGE2 inhibition) were comparable to the reference drugs. Molecular docking revealed potential preferable binding to the active sites of cyclooxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) enzymes. This study provides the first evidence that benzophenone–thiazole hybrids may also dock in mPGES-1, a new attractive anti-inflammatory drug target, besides providing promising ex vivo anti-inflammatory activity. Thus, the novel hybrids are promising anti-inflammatory lead compounds and highlight the significance of optimal substituent selection in the design of potent PGE2 inhibitors.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451189","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}

引用次数: 0