European Journal of Medicinal Chemistry最新文献

{"title":"Discovery and structure-activity relationship studies of novel α-ketoamide derivatives targeting the SARS-CoV-2 main protease","authors":"Chong Huang ,&nbsp;Rui Zeng ,&nbsp;Jingxin Qiao ,&nbsp;Baoxue Quan ,&nbsp;Ronghua Luo ,&nbsp;Qiao Huang ,&nbsp;Nihong Guo ,&nbsp;Yueyue Li ,&nbsp;Xinyan Long ,&nbsp;Ronggang Ma ,&nbsp;Anjie Xia ,&nbsp;Zhen Fang ,&nbsp;Yifei Wang ,&nbsp;Yueshan Li ,&nbsp;Yongtang Zheng ,&nbsp;Linli Li ,&nbsp;Jian Lei ,&nbsp;Shengyong Yang","doi":"10.1016/j.ejmech.2023.115657","DOIUrl":"10.1016/j.ejmech.2023.115657","url":null,"abstract":"<div><p><span>The SARS-CoV-2 main protease (M</span>^pro, also named 3CL^pro) is a promising antiviral target against COVID-19 due to its functional importance in viral replication and transcription. Herein, we report the discovery of a series of α-ketoamide derivatives as a new class of SARS-CoV-2 M^pro inhibitors. Structure-activity relationship (SAR) of these compounds was analyzed, which led to the identification of a potent M^pro inhibitor (<strong>27h</strong>) with an IC₅₀ value of 10.9 nM. The crystal structure of M^pro in complex with <strong>27h</strong> revealed that α-ketoamide warhead covalently bound to Cys145s of the protease. In an <em>in vitro</em> antiviral assay, <strong>27h</strong> showed excellent activity with an EC₅₀<span> value of 43.6 nM, comparable to the positive control, Nirmatrelvir. This compound displayed high target specificity for M</span>^pro<span> against human proteases and low toxicity. It also possesses favorable pharmacokinetic properties. Overall, compound </span><strong>27h</strong><span> could be a promising lead compound for drug discovery targeting SARS-CoV-2 M</span>^pro and deserves further in-depth studies.</p></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"259 ","pages":"Article 115657"},"PeriodicalIF":6.7,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10094899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conjugation of antimicrobial peptides to enhance therapeutic efficacy","authors":"Sanjay Prasad Selvaraj ,&nbsp;Jyh-Yih Chen","doi":"10.1016/j.ejmech.2023.115680","DOIUrl":"10.1016/j.ejmech.2023.115680","url":null,"abstract":"<div><p><span><span>The growing prevalence of antimicrobial resistance (AMR) has brought with it a continual increase in the numbers of deaths from multidrug-resistant (MDR) infections. Since the current arsenal of antibiotics has become increasingly ineffective, there exists an urgent need for discovery and development of novel antimicrobials. </span>Antimicrobial peptides<span> (AMPs) are considered to be a promising class of molecules due to their broad-spectrum activities and low resistance rates compared with other types of antibiotics. Since AMPs also often play major roles in elevating the host immune response, the molecules may also be called “host defense peptides.” Despite the great promise of AMPs, the majority remain unsuitable for clinical use due to issues of structural instability, degradation by proteases, and/or toxicity to host cells. Moreover, AMP activities </span></span><em>in vivo</em><span><span><span> can be influenced by many factors, such as interaction with blood and serum biomolecules, physiological salt concentrations or different pH values. To overcome these limitations, structural modifications can be made to the AMP. Among several modifications, physical and chemical conjugation of AMP to other biomolecules is widely considered an effective strategy. In this review, we discuss structural modification strategies related to conjugation of AMPs and their possible effects on mode of action. The conjugation of fatty acids, glycans, antibiotics, </span>photosensitizers, polymers, </span>nucleic acids<span>, nanoparticles, and immobilization to biomaterials are highlighted.</span></span></p></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"259 ","pages":"Article 115680"},"PeriodicalIF":6.7,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10393988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and optimization of 2,3-diaryl-1,3-thiazolidin-4-one-based derivatives as potent and selective cytotoxic agents with anti-inflammatory activity","authors":"Ahmed M. Shawky ,&nbsp;Faisal A. Almalki ,&nbsp;Ashraf N. Abdalla ,&nbsp;Bahaa G.M. Youssif ,&nbsp;Maha M. Abdel-Fattah ,&nbsp;Fatima Hersi ,&nbsp;Hany A.M. El-Sherief ,&nbsp;Nashwa, A. Ibrahim ,&nbsp;Ahmed M. Gouda","doi":"10.1016/j.ejmech.2023.115712","DOIUrl":"10.1016/j.ejmech.2023.115712","url":null,"abstract":"<div><p><span>Several studies have indicated the potential therapeutic outcomes of combining selective COX-2 inhibitors with tubulin-targeting anticancer agents. In the current study, a novel series of thiazolidin-4-one-based derivatives (</span><strong>7a–q</strong><span>) was designed by merging the pharmacophoric features of some COXs inhibitors and tubulin polymerization inhibitors. Compounds </span><strong>7a–q</strong> were synthesized and evaluated for their cytotoxic activity against MCF7, HT29, and A2780 cancer cell lines (IC₅₀ = 0.02–17.02 μM). The cytotoxicity of <strong>7a–q</strong> was also assessed against normal MRC5 cells (IC₅₀ = 0.47–13.46 μM). Compounds <strong>7c</strong>, <strong>7i</strong>, and <strong>7j</strong><span>, the most active in the MTT assay, significantly reduced the number of HT29 colonies compared to the control. Compounds </span><strong>7c</strong>, <strong>7i</strong>, and <strong>7j</strong><span> also induced significant decreases in the tumor volumes and masses in Ehrlich solid carcinoma-bearing mice compared to the control. The three compounds also exhibited significant anti-HT29 migration activity in the wound-healing assay. They have also induced cell cycle arrest in HT29 cells at the S and G</span>₂/M phases. In addition, they induced significant increases in both early and late apoptotic events in HT29 cells compared to the control, where <strong>7j</strong> showed the highest effect. On the other hand, compound <strong>7j</strong><span> (1 μM) displayed weak inhibitory activity against tubulin polymerization compared to colchicine (3 μM). On the other hand, compounds </span><strong>7a</strong>–<strong>q</strong> inhibited the activity of COX-2 (IC₅₀<span> = 0.42–29.11 μM) compared to celecoxib (IC</span>₅₀ = 0.86 μM). In addition, <strong>7c</strong>, <strong>7i</strong>, and <strong>7j</strong><span><span> showed moderate inhibition of inflammation in rats compared to indomethacin, with better GIT safety profiles. </span>Molecular docking analysis revealed that </span><strong>7c</strong>, <strong>7i</strong>, and <strong>7j</strong><span> have higher binding free energies towards COX-2 than COX-1. These above results suggested that </span><strong>7j</strong> could serve as a potential anticancer drug candidate.</p></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"259 ","pages":"Article 115712"},"PeriodicalIF":6.7,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10394503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of novel bosentan analogues as endothelin receptor antagonists for pulmonary arterial hypertension","authors":"Jigar Panchal ,&nbsp;Shivangi Jaiswal ,&nbsp;Sonika Jain ,&nbsp;Jyoti Kumawat ,&nbsp;Ashima Sharma ,&nbsp;Pankaj Jain ,&nbsp;Smita Jain ,&nbsp;Kanika Verma ,&nbsp;Jaya Dwivedi ,&nbsp;Swapnil Sharma","doi":"10.1016/j.ejmech.2023.115681","DOIUrl":"10.1016/j.ejmech.2023.115681","url":null,"abstract":"<div><p><span><span><span>Since decades, bosentan has been in use for the treatment of </span>pulmonary arterial hypertension<span> (PAH). However, chronic exposure to bosentan leads to the development of resistance, tolerance, and serious adverse effects that have restricted its usage in clinical practices. To surmount these limitations, some new bosentan derivatives have been synthesized and evaluated for their therapeutic efficacy in PAH. Molecular docking analyses of all the synthesized derivatives were carried out using the </span></span>endothelin<span> (ET) receptor. In addition, the inhibitory ability of synthesized derivatives was determined in in vitro assay employing an ET-1 human ELISA kit. Among the synthesized derivatives, three derivatives namely 17d, 16j, and 16h with higher docking scores and lower IC50 values were selected for determination of the magnitude of the binding force between the derivative and ET receptor using molecular dynamics (MD) simulations study. Further, these derivatives were subjected to </span></span>in vivo studies<span><span> using monocrotaline (MCT) induced PAH in rat model. Results of in vivo studies inferred that the derivatives exhibit impressive ability to reduce PAH. Besides, its protective role was also evidenced in </span>hemodynamic<span><span> and right ventricular hypertrophy analyses, histological analysis, cardiac biomarkers, hypoxia-inducible factor 1 alpha (HIF1α) levels, and biochemical studies. Furthermore, gene quantification by quantitative RT-PCR and </span>Western blot analysis was also performed to examine its effect on the expression of key proteins in PAH.</span></span></p><p>Notably, amongst three, derivative <strong>16h</strong> exhibited the most encouraging results in molecular docking analysis, <em>in vitro</em><span><span>, in vivo, histopathological, biochemical, protein expression, and </span>MD studies. Besides, derivative </span><strong>16h</strong><span> also showed impressive pharmacokinetic features in ADMET analysis.</span></p><p>In conclusion, derivative 16 h could act as a reliable ET receptor antagonist and requires further exploration to attain its therapeutic utility in PAH management.</p></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"259 ","pages":"Article 115681"},"PeriodicalIF":6.7,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10412905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of novel celastrol-ligustrazine hybrids as potent peroxiredoxin 1 inhibitors against lung cancer","authors":"Ying Bai ,&nbsp;Chao Liang ,&nbsp;Jiawei Zhou ,&nbsp;Yafeng Liu ,&nbsp;Fengxuan Wang ,&nbsp;Jian Gao ,&nbsp;Jing Wu ,&nbsp;Dong Hu","doi":"10.1016/j.ejmech.2023.115656","DOIUrl":"10.1016/j.ejmech.2023.115656","url":null,"abstract":"<div><p><span><span>The disruption of oxidation-reduction equilibrium through inhibiting reactive oxygen species (ROS) clearance or enhancing ROS production has emerged as a novel and promising strategy for cancer therapy. Herein, a series of celastrol-ligustrazine hybrids were designed and synthesized as effective ROS promoters, and their </span>biological activities were further evaluated. Among them, compound </span><strong>7e</strong><span> stood out as the most potent peroxiredoxin 1 (PRDX1) inhibitor (IC</span>₅₀ = 0.164 μM), which was significant super to the recognized PRDX1 inhibitor Conoidin A (IC₅₀<span> = 14.80 μM) and the control compound celastrol (IC</span>₅₀ = 1.622 μM). Furthermore, <strong>7e</strong> dramatically promoted intracellular ROS accumulation, and inhibited the proliferation, invasion and migration of cancer cells besides inducing apoptosis <em>in vitro</em>. Additionally, <strong>7e</strong><span> suppressed the key signaling pathways (AKT and ERK) and promoted the expression of apoptosis-related proteins (cleaved caspase-3/8 and cleaved PARP) in A549 cells, which resulted in the prevention of tumor progression. Most importantly, compound </span><strong>7e</strong> (TGI = 77.47%) showed more considerable <em>in vivo</em><span> antitumor efficacy and less toxicity than celastrol (TGI = 71.00%). Overall, this work indicates </span><strong>7e</strong> as the most potential PRDX1 inhibitor and may be a promising candidate for the therapy of lung cancer.</p></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"259 ","pages":"Article 115656"},"PeriodicalIF":6.7,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10499282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in medicinal chemistry of Neglected Tropical Diseases (NTDs)","authors":"Edeildo Ferreira da Silva-Júnior,&nbsp;Peng Zhan","doi":"10.1016/j.ejmech.2023.115714","DOIUrl":"10.1016/j.ejmech.2023.115714","url":null,"abstract":"","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"259 ","pages":"Article 115714"},"PeriodicalIF":6.7,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10095360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of triazole-bridged aryl adamantane analogs as an intriguing class of multifunctional agents for treatment of Alzheimer's disease","authors":"Gopichand Gutti ,&nbsp;Jennifer Leifeld ,&nbsp;Ramakrishna Kakarla ,&nbsp;Nilesh Gajanan Bajad ,&nbsp;Ankit Ganeshpurkar ,&nbsp;Ashok Kumar ,&nbsp;Sairam Krishnamurthy ,&nbsp;Christina Klein-Schmidt ,&nbsp;Daniel Tapken ,&nbsp;Michael Hollmann ,&nbsp;Sushil Kumar Singh","doi":"10.1016/j.ejmech.2023.115670","DOIUrl":"10.1016/j.ejmech.2023.115670","url":null,"abstract":"<div><p><span><span><span>Alzheimer's disease (AD) is a progressive brain disorder associated with slow loss of brain functions leading to memory failure and modest changes in behavior. The multifactorial neuropathological condition is due to a depletion of </span>cholinergic neurons and accumulation of amyloid-beta (Aβ) plaques. Recently, a multi-target-directed ligand (MTDL) strategy has emerged as a robust </span>drug discovery<span> tool to overcome current challenges. In this research work, we aimed to design and develop a library of triazole-bridged aryl adamantane analogs for the treatment of AD. All synthesized analogs were characterized and evaluated through various </span></span><em>in vitro</em> and <em>in vivo</em> biological studies. The optimal compounds <strong>32</strong> and <strong>33</strong><span> exhibited potent inhibitory activities against acetylcholinesterase (AChE) (</span><strong>32</strong> - IC₅₀ = 0.086 μM; <strong>33</strong> - 0.135 μM), and significant Aβ aggregation inhibition (20 μM). N-methyl-<span>d</span>-aspartate (NMDA) receptor (GluN1-1b/GluN2B subunit combination) antagonistic activity of compounds <strong>32</strong> and <strong>33</strong><span> measured upon heterologous expression in </span><span><em>Xenopus laevis</em></span> oocytes showed IC₅₀<span> values of 3.00 μM and 2.86 μM, respectively. The compounds possessed good blood-brain barrier permeability in the PAMPA<span> assay and were safe for SH-SY5Y neuroblastoma (10 μM) and HEK-293 cell lines (30 μM). Furthermore, </span></span><em>in vivo</em> behavioral studies in rats demonstrated that both compounds improved cognitive and spatial memory impairment at a dose of 10 mg/kg oral administration. Together, our findings suggest triazole-bridged aryl adamantane as a promising new scaffold for the development of anti-Alzheimer's drugs.</p></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"259 ","pages":"Article 115670"},"PeriodicalIF":6.7,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10116697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small molecule inhibitors of NLRP3 inflammasome and GSK-3β in the management of traumatic brain injury: A review","authors":"Mahammad Ghouse Shaik ,&nbsp;Swanand Vinayak Joshi ,&nbsp;Ravikumar Akunuri ,&nbsp;Preeti Rana ,&nbsp;Ziaur Rahman ,&nbsp;Anusha Polomoni ,&nbsp;Venkata Madhavi Yaddanapudi ,&nbsp;Manoj P. Dandekar ,&nbsp;Nanduri Srinivas","doi":"10.1016/j.ejmech.2023.115718","DOIUrl":"10.1016/j.ejmech.2023.115718","url":null,"abstract":"<div><p><span><span>Traumatic brain injury (TBI) is a debilitating mental condition which causes physical disability and morbidity worldwide. TBI may damage the brain by direct injury that subsequently triggers a series of neuroinflammatory events. The activation of </span>NLRP3<span> inflammasome<span> and dysregulated host immune system has been documented in various neurological disorders such as TBI, </span></span></span>ischemic stroke<span><span> and multiple sclerosis<span>. The activation of NLRP3 post-TBI increases the production of pro-inflammatory cytokines and caspase-1, which are major drivers of neuroinflammation<span> and apoptosis. Similarly, GSK-3β regulates apoptosis through tyrosine kinase and canonical </span></span></span>Wnt signalling pathways<span>. Thus, therapeutic targeting of NLRP3 inflammasome and GSK-3β has emerged as promising strategies for regulating the post-TBI neuroinflammation and neurobehavioral disturbances. In this review, we discuss the identification &amp; development of several structurally diverse and pharmacologically interesting small molecule inhibitors for targeting the NLRP3 inflammasome and GSK-3β in the management of TBI.</span></span></p></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"259 ","pages":"Article 115718"},"PeriodicalIF":6.7,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10036093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and evaluation of novel pleuromutilin aryl acrylate derivatives as promising broad-spectrum antibiotics especially for combatting multi-drug resistant gram-negative bacteria","authors":"Min Li ,&nbsp;Jialin Li ,&nbsp;Jingyi Li ,&nbsp;Jie Zhang ,&nbsp;Yuqing Zhao ,&nbsp;Wenying Li ,&nbsp;Yunfei Zhang ,&nbsp;Jinrong Hu ,&nbsp;Xiaolin Xie ,&nbsp;Dezhu Zhang ,&nbsp;Han Li ,&nbsp;Qianqian Zhao ,&nbsp;Hong Gao ,&nbsp;Chengyuan Liang","doi":"10.1016/j.ejmech.2023.115653","DOIUrl":"10.1016/j.ejmech.2023.115653","url":null,"abstract":"<div><p><span><span><span>The emergence of drug-resistant strains presents a grave challenge for traditional antibiotics, underscoring the exigency of exploring novel antibacterial drugs. To address this, the present study endeavors to design and synthesize a collection of </span>pleuromutilin aromatic </span>acrylate<span> derivatives, guided by combination principles. The antibacterial activity and structure-activity relationship of these derivatives were evaluated, and most of the derivatives displayed moderate to excellent antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria. Among these derivatives, </span></span><strong>5g</strong> exhibited the strongest antibacterial activity, with MIC (minimum inhibitory concentration) values ranging from <strong>1</strong>–<strong>32 μg/mL</strong>, and a MIC value against clinically isolated drug-resistant strains of <strong>4</strong>–<strong>64 μg/mL</strong>. Additionally, <strong>5g</strong><span> exhibited negligible cytotoxicity, superior anti-mycoplasma activity, and a greater propensity to perturb bacterial cell membranes. Notably, the administration of </span><strong>5g</strong> resulted in an increased survival rate of MRSA (Methicillin-resistant <em>Staphylococcus aureus</em>)-infected mice, with an ED₅₀ (median effective dose) value of <strong>9.04 mg/kg</strong>. These results indicated the potential of <strong>5g</strong> to be further developed as an antibacterial drug for the clinical treatment of drug-resistant bacterial infections.</p></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"259 ","pages":"Article 115653"},"PeriodicalIF":6.7,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10037658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in triazoles as tyrosinase inhibitors","authors":"Arif Mermer ,&nbsp;Serpil Demirci","doi":"10.1016/j.ejmech.2023.115655","DOIUrl":"10.1016/j.ejmech.2023.115655","url":null,"abstract":"<div><p>The tyrosinase<span><span><span><span> enzyme, which is widely found in microorganisms, animals and plants, has a significant position in </span>melanogenesis<span>, plays an important role in undesirable browning of fruits and vegetables, antibiotic resistance, skin pigment formation, sclerotization of cuticle, </span></span>neurodegeneration<span><span>, etc. Therefore, with the wide potential application fields of tyrosinase in food, agriculture, cosmetics and pharmaceutical industries, which has become the target enzyme for the development of therapeutic agents such as antibrowning, </span>anticancer<span><span>, antibacterial, skin whitening, insecticides, etc., a large number of synthetic tyrosinase inhibitors have been widely reported in recent years. The </span>triazole ring, which has a broad spectrum of biological action, is of increasing interest in the synthesis of new tyrosinase inhibitors. In this review, tyrosinase inhibition effects, structure-activity relationships, enzyme </span></span></span>inhibition kinetics and mechanisms of action of 1,2,3- or 1,2,4-triazole derivatives were investigated. The data gathered is anticipated to supply rational guidance and an influential strategy for the development of novel, potent and safe tyrosinase inhibitors for better practical application in the future.</span></p></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"259 ","pages":"Article 115655"},"PeriodicalIF":6.7,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10181419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}