Anti-cancer agents in medicinal chemistry最新文献

{"title":"Preliminary Investigations on Acyl Hydrazones Bearing Sulfonamides as Inhibitors of the Human Carbonic Anhydrase Isoforms I, II, IX, and XII.","authors":"Efe Doğukan Dincel, Ebru Didem Kuran, Abdulilah Ece, Faika Başoğlu-Ünal, Gioele Renzi, Gloria Badii, Fabrizio Carta, Cladiu T Supuran, Nuray Ulusoy-Güzeldemirci","doi":"10.2174/0118715206356980250113074705","DOIUrl":"https://doi.org/10.2174/0118715206356980250113074705","url":null,"abstract":"<p><strong>Aim: </strong>The present study aims to identify the synthesis and structural characterization of acyl hydrazone- sulfonamide-containing compounds that were tested in vitro on human carbonic anhydrase (hCA) isoforms I, II, IX, and XII.</p><p><strong>Methods: </strong>Herein, acyl hydrazone derivatives containing the primary sulfonamide moiety were synthesized via a three-step synthetic pathway starting from the commercially available 4-sulfamoyl benzoic acid. Structural characterizations of the final compounds were assessed through IR IR, 1H-NMR, 13C-NMR, and elemental analyses. The in vitro profiling activity of the final compounds on the Carbonic Anhydrases (CAs; EC 4.2.1.1) I, II, IX, and XII were performed by means of the stopped-flow technique and revealed nanomolar inhibitory potencies on the selected targets. Molecular docking and molecular dynamic simulations afforded a detailed understanding of the binding modes of the most effective compounds.</p><p><strong>Results: </strong>We reported the synthesis and structural characterization of 25 acyl hydrazone-sulfonamide-containing compounds that were tested in vitro on the hCAs I, II, IX, and XII isoforms for their inhibitory features. Overall, all compounds showed nanomolar inhibition potencies on the panel of hCAs considered, and their binding modes were deciphered by means of in-silico studies. Molecular docking followed by MD simulations confirmed the stability of 4l-hCA I, 4n-hCA II, 4t-hCA II, 4v-hCA XII, and 4w-hCA XII complexes.</p><p><strong>Conclusion: </strong>This study presents a deep understanding of the structural determinants influencing the affinity and selectivity of the designed compounds towards different hCAs, thus offering valuable insights for further optimization and development in the field.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514421","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":"Melittin, A Potential Game-changer in the Fight Against Breast Cancer: A Systematic Review.","authors":"Gilles Prince, Ahmad Assi, Marc Aoude, Hampig Raphael Kourie, Fadi Haddad","doi":"10.2174/0118715206347581250217045306","DOIUrl":"https://doi.org/10.2174/0118715206347581250217045306","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer is the most common cancer in women. Traditional treatments include endocrine therapy, chemotherapy, surgery, radiation, and immunotherapy. Recent studies suggest melittin, a component of bee venom, as a promising breast cancer treatment due to its anticancer properties: inducing cytotoxicity, apoptosis, and gene regulation.</p><p><strong>Method: </strong>This manuscript aims to review melittin's potential therapeutical and future implications in treating breast cancer. An extensive literature search was conducted on MEDLINE and Cochrane databases up to July 2024 using Boolean operators with a combination of keywords. After screening, data extraction, and descriptive analysis, 40 articles were retained.</p><p><strong>Results: </strong>Experimental data and different therapeutical strategies were collected. Melittin disrupts tumor cell membranes and modulates key apoptotic pathways. Advanced delivery systems enhance their effectiveness and reduce toxicity. Combining melittin with chemotherapy shows synergistic effects, improving outcomes. Thus, melittin could be a valuable addition to breast cancer therapies.</p><p><strong>Conclusion: </strong>Further clinical trials are essential to validate its potential and establish its role in breast cancer therapy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514458","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":"The Kinesin Eg5 Inhibitor K858 Enhances Radiosensitivity in Esophageal Squamous Cell Carcinoma and Affects the Expression of Epithelial-mesenchymal Transition Related Markers: In vitro and In vivo Studies.","authors":"Ruixue Liu, Zhijun Yu, Wenbin Shen, Shuchai Zhu","doi":"10.2174/0118715206373782250211104402","DOIUrl":"https://doi.org/10.2174/0118715206373782250211104402","url":null,"abstract":"<p><strong>Background: </strong>Radioresistance is the primary cause of treatment failure in esophageal squamous cell carcinoma, emphasizing the importance of identifying effective radiosensitizers.</p><p><strong>Objectives: </strong>This study aimed to explore the effects and potential mechanisms of Eg5 inhibitor K858 on the radiosensitivity of esophageal squamous cell carcinoma TE-1 and KYSE150 cell lines, as well as xenografts (TE-1 cells).</p><p><strong>Methods: </strong>Cellular function was assessed using CCK8, wound healing, and transwell invasion assays. Radiosensitivity parameters were derived from colony formation assays. Cell apoptosis and cell cycle were assessed using flow cytometry, whereas protein expression levels were detected using western blotting and immunohistochemistry. The xenograft model was used to observe the growth of tumors.</p><p><strong>Results: </strong>K858 inhibited the malignant functions of TE-1 and KYSE150 cell lines. Radiosensitivity parameters were reduced after K858 treatment. The combination of K858 and irradiation markedly suppressed cell proliferation, induced apoptosis, and stimulated cell cycle arrest during the irradiation-sensitive phase. Additionally, K858, combined with irradiation, significantly increased the expression of the epithelial-mesenchymal transition marker E-cadherin and decreased the expression of N-cadherin, vimentin, MMP2, and MMP9. K858, combined with irradiation, significantly inhibited tumor growth in xenograft models.</p><p><strong>Conclusion: </strong>K858 enhanced the radiosensitivity of esophageal squamous cell carcinoma and affected the expression of epithelial-mesenchymal transition-related markers.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490537","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":"Atractylenolide I Inhibits the Growth of Esophageal Cancer Cells by Inhibiting the Wnt/Β-Catenin Pathway.","authors":"Maowei Lian, Yunxiang Zhang, Xu Li, Na Niu, Dong Tang, Lihua Cao, Yong Li, Xiaocong Xiang, Chunlei Yu","doi":"10.2174/0118715206366543250213071529","DOIUrl":"https://doi.org/10.2174/0118715206366543250213071529","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer is a highly lethal cancer with a rapidly increasing incidence and a poor prognosis. Atractylenolide I is a natural sesquiterpene lactone extracted from the rhizome of the Asteraceae plant, which has a variety of pharmacological effects, such as anti-inflammatory and immunomodulatory. Still, its impact on esophageal cancer has not been reported. Therefore, this study investigated the in vitro and in vivo effects of Atractylenolide I on the growth and proliferation of esophageal cancer and explored its possible mechanisms.</p><p><strong>Methods: </strong>To evaluate the effect of atractylenolide I on esophageal cancer cells, apoptosis assay and cell cycle assay tests were performed. Atractylenolide I was used to treat esophageal cancer cells for 48 hours, and flow cytometry detects apoptosis and cell cycle. The Wnt/β-catenin-related pathway proteins were then detected by Western blotting. For in vivo studies, an esophageal cancer graft tumor model was established subcutaneously in BALB/c nude mice, which were given Atractylenolide I treatment for 2 weeks.</p><p><strong>Result: </strong>The result shows that Atractylenolide I inhibited the proliferation and induced apoptosis of esophageal squamous carcinoma and adenocarcinoma cells. Further research shows that Atractylenolide I inhibited the Wnt/β-catenin signaling pathway, decreased the expression of CCND1, MYC, and FN1 genes, and thus increased the apoptosis of esophageal cancer cells and blocked the cell cycle in G0/G1 phase, hence exerting the role of inhibiting esophageal cancer cells in vivo and in vitro.</p><p><strong>Conclusion: </strong>This study indicates that Atractylenolide I is an efficient lead compound for the treatment of esophageal cancer, providing a theoretical basis for further clinical development and application of Atractylenolide I.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466796","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":"CDH1-involved Ubiquitination of SIRT5 Promotes the Entry of Colorectal Cancer Cells into Quiescence and Enhances Cell Stemness.","authors":"Wei Li, Jian Chen, Jinbao Yang, Bo Zhang, Dihao Wen, Zhibin Jiang","doi":"10.2174/0118715206336851241204111721","DOIUrl":"https://doi.org/10.2174/0118715206336851241204111721","url":null,"abstract":"<p><strong>Background: </strong>This study explored whether the cell cycle regulator cadherin 1 (CDH1) impacts colorectal cancer cell cycle and stemness via mediating ubiquitination of sirtuin 5 (SIRT5).</p><p><strong>Methods: </strong>We first constructed CDH1 overexpression plasmid and small interfering RNA against SIRT5 (siSIRT5) and transfected them into HCT116/HT29 cells, followed by transfection efficiency verification. The effect of CDH1 on Cyclin F/SIRT5/CDH1 protein levels in HCT116/HT29 cells was verified by Western blot. After up-regulation of CDH1, changes in SIRT5 ubiquitination (immunoprecipitation), cell cycle (cell cycle kit), proliferation (5-Bromodeoxyuridine assay), and stemness marker expressions (qRT-PCR) in HCT116/HT29 cells were detected. Rescue assays were performed to examine cell proliferation and stemness marker expressions.</p><p><strong>Results: </strong>Overexpression of CDH1 decreased Cyclin F expression and increased SIRT5 and CDH1 expressions in HCT116/HT29 cells. Up-regulation of CDH1 suppressed SIRT5 ubiquitination, promoted G0/G1 phase blockage in HCT116/HT29 cells, boosted cell proliferation into quiescence and enhanced cell stemness. siSIRT5 counteracted the regulatory effect of CDH1 overexpression on colorectal cancer cells.</p><p><strong>Conclusion: </strong>CDH1 promotes the entry of colorectal cancer cells into quiescence and enhances stemness by dampening SIRT5 ubiquitination.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405058","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":"Recurrent Missense Driver STAT5B N642H Mutation in Children Transiting into Adolescence, with Acute Lymphoid Leukemia and its In silico Inhibition.","authors":"Rehana Yasmin, Rashda Abbasi, Tajdar Jahangir Gohar, Hina, Nafees Ahmad, Sajid Malik","doi":"10.2174/0118715206350463241226032324","DOIUrl":"https://doi.org/10.2174/0118715206350463241226032324","url":null,"abstract":"<p><strong>Background: </strong>The occurrence of gain of function mutations in STAT5B has been associated to survival, and drug resistance in Leukemia. In silico screening of compounds having inhibitory potential towards mutated proteins, can be helpful in the development of specific inhibitors.</p><p><strong>Objective: </strong>This study was designed to screen selected JAK-STAT mutations in leukemia patients and virtual exploration of molecular interaction of potential inhibitors with their mutated products.</p><p><strong>Methods: </strong>In total 276 patients were randomly recruited for this study. Demographic and clinical data were summarized. The genetic status of JAK1V623A, JAK2 S473 and STAT5BN642H were screened through allele specific PCR. In-silico analysis was performed on wild type and mutant protein sequences retrieved from Protein databank. The ligands and protein were prepared through standard protocols, and docking was performed through Auto Dock Vina 1.2.0.</p><p><strong>Results: </strong>Acute lymphoblastic leukemia comprises 70% of the total patients. Male to female ratio was 3:1. All the patients were homozygous for JAK1V623A, JAK2 S473 major allele. However, 6 patients (5 male, 1 female) with ALL were STAT5BN642H+. The molecular docking of the ligands to wild type and STAT5BN642H+revealed that AC- 4-130, Pimozide, Indirubin and Stafib-2 have higher but differential docking affinities for SH2-domain of both normal and mutated STAT5B. However, AC-4-130 has a higher affinity for wild type and Stafib-2 has stable molecular interaction with STAT5BN642H+.</p><p><strong>Conclusion: </strong>The aggressive form of pediatric leukemia, carrying STAT5BN642H+ mutation is identified in the studied population. It is predicted that AC-14-30 and stafib-2 have potential for inhibition of constitutively active STAT5B if optimized for use in combination therapy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490536","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":"In-silico and In-vitro Molecular Analysis of Oleanolic Acid and Cisplatin on Pancreatic Cancer (Panc-1 Cell Line).","authors":"Srimathi Devi Jegannathan, Wishwaa Jayapal, Bindhu Jayaprakash, Teena Prabhu","doi":"10.2174/0118715206336591241112061246","DOIUrl":"https://doi.org/10.2174/0118715206336591241112061246","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cisplatin (CIS) is a standard chemotherapeutic drug currently used for various cancer treatments. Due to its chemo-resistance and toxic effects, a new combinatorial approach was preferred. Oleanolic acid is one such pentacyclic terpenoid compound that tends to have various anti-cancer properties against a wide range of human carcinoma models. Yet, the final mechanisms of individual and Combinational Treatment of OA and CIS on pancreatic carcinoma persist indescribable.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The Current study analyses the in-silico and in-vitro Molecular efficacy of the combinational dose of OA and CIS in Pancreatic cancer using the Panc-1 cell line.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and material: &lt;/strong&gt;The preliminary screening of the anti-cancer effect of OA and CIS was evaluated meticulously using docking score with Auto-Dock. For further in-vitro analysis of the ligand, OA was isolated from blueberry through ultrasonication extraction, followed by a comprehensive range of qualitative and quantitative analysis by chromatography techniques and GC-MS studies. Anti-proliferative and cytotoxicity activity of our combinational compounds were determined using the MTT assay and the LDH leakage assay. Cell membrane integrity was analyzed by measuring ROS generation and mitochondrial membrane potential in treated cells using fluorometric detection methods. Detection of the Anti-Apoptotic potential of our target compound was evaluated by DNA fragmentation assay and Caspase activity assay. Quantitative real-time PCR and Western Blotting were used to determine the genes and Protein expression intricated for apoptosis, angiogenesis, cell cycle regulation, and metastasis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Molecular docking analysis suggests that OA and CIS possess a strong binding affinity for hydrogen bond interaction with the highest fitness score for various anti-cancer genes, leading to the drug's significant apoptotic and anti-angiogenic effects. Further preliminary analysis reports of UV spectra and GC-MS data suggested that the OA compound tends to exhibit a peak at 235-288 nm with a GC retention time of 15.45 min with m/z 240 and m/z 280 ratios. The output of In-vitro analysis of the anti-proliferative and cytotoxicity effect of OA and CIS tends to show the significant inhibition of cells in a dose-dependent manner with IC50 value of 5.75 μM OA and 2.95 μM of CIS with significant leakage in LDH was observed in combinational treated cells compare to individual treated cancer cells. The computational CI plot report of OA and CIS report revealed a synergistic dose effect with a CI value&lt;1. Apoptotic effect of combinational dose revealed synergistic effects by down-regulation of angiogenic and metastatic genes and proteins (CDKN2A, SMAD4, VEG-F, MMP-9) stimulates to caspase cascade activation by intrinsic mediated apoptosis, which was further confirmed through DNA fragmentation assay by cleavage of fragments in treated ce","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389771","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":"Virtual Screening and Biological Evaluation of T22306 as a Potent Third-generation EGFR Inhibitor for NSCLC Treatment.","authors":"Ran Wang, Wei Ruan, Dang Fan, Li Long, Han Zhang, Min Li, Shan Xu, Linxiao Wang","doi":"10.2174/0118715206362954250203103859","DOIUrl":"https://doi.org/10.2174/0118715206362954250203103859","url":null,"abstract":"<p><strong>Objectives: </strong>According to the data, mutations in EGFR-related genes are the main cause of Non-Small Cell Lung Cancer (NSCLC), necessitating the development of new drug constructs for EGFR-TKIs particularly important. This study aimed to screen potential third-generation EGFR-TKIs to address the emerging drug resistance challenges in NSCLC.</p><p><strong>Methods: </strong>In this study, virtual screening, molecular dynamics modeling, and bioactivity evaluation were carried out to find a potential EGFR inhibitor that could overcome the L858R/T790M mutation. At first, 12 potential compounds were screened step by step from about 250,000 structures by virtual screening. These 12 compounds were subjected to MTT antitumor activity evaluation and kinase inhibition assay to select compounds with strong antiproliferative effects on cancer cells. Then, the preferred compounds were subjected to time-dependent assay, scratch assay, AO staining assay, and hemolysis assay. Finally, the preferred compound was subjected to molecular docking and molecular dynamics simulation with 5HG7 protein.</p><p><strong>Result: </strong>The IC50 of T22306 on H1975 cells was 9.17 μM. In further kinase evaluation, the kinase inhibition of EGFRL858R/T790M was 69.17%. In addition, time-dependent experiments and scratch and AO staining assays confirmed the potential of T22306 as an EGFR-TKI inhibitor, while hemolysis assays demonstrated no significant toxicity. Finally, molecular docking revealed the formation of critical hydrogen bonds between T22306 and LEU-718. Furthermore, molecular dynamics simulations showed that the T22306-5HG7 complex has a low binding energy (-117.73 ± 18.69 kJ/mol), thus suggesting that T22306 binds tightly to the target protein 5HG7.</p><p><strong>Conclusion: </strong>In this study, we rapidly screened potential compounds against NSCLC with the help of virtual screening technology. Further in vitro experiments demonstrated that T22306 successfully overcame the L858R/T790M mutation and could be a potential epidermal growth factor receptor inhibitor.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389772","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":"An Insight into Research Advances on Herbal and Phytochemical Approaches to the Management of Hepatocellular Carcinoma from January 2020 to July 2024.","authors":"Zulfa Nooreen, Sunil Harer, Awani Kumar Rai, Ankita Wal, Deepak Nathiya, Parjinder Kaur","doi":"10.2174/0118715206348951241120120918","DOIUrl":"https://doi.org/10.2174/0118715206348951241120120918","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular Carcinoma (HCC) is a primary hepatic tumor and is one of the world's third most frequent malignancies after lung and colorectal. After stomach, lung, and colorectal cancers, it is the most common cause of cancer-related mortality. Since the Palaeolithic era, herbs have been used as an essential source of alternative drugs. Modern cancer treatments that use chemotherapeutic medications are made of chemicals derived from plants.</p><p><strong>Objective: </strong>The present review is about the compilation of phytochemical extracts and molecules from 2020 to July 2024.</p><p><strong>Methods: </strong>A detailed literature survey was conducted to compile data from PubMed, Sci Finder, Science Direct, Google, etc. Results: The identification of novel treatments and their combinations for usage in the adjuvant context potentially address significant unmet needs in the management of HCC. A large number of investigations have been carried out these days on plants. Numerous phytochemicals included in plant extract may possess anti-cancer properties, including the ability to induce cell cycle arrest, suppress cell proliferation, increase apoptosis, and obstruct migration, invasion, and metastasis. These approaches possess less hazardous and more effective treatment in HCC.</p><p><strong>Conclusion: </strong>This article is the compilation of data about research on phytomolecules and herbal extracts from January 2020 to July 2024 for the treatment of HCC in vitro and in-vivo. Various mechanisms involved in the treatment are also explored in the article. The growing interest of researchers in investigating new approaches toward HCC management with phytomolecules is rapidly growing.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397996","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":"A Systematic Quantitative Approach to Rational Drug Design and the Discovery of Novel Human Antigen R (HuR) Inhibitors.","authors":"Juhi Dey, Kumari Kaushiki, K M Abha Mishra, Paga Sudheer, Kalyan Kumar Sethi","doi":"10.2174/0118715206354755241220062707","DOIUrl":"https://doi.org/10.2174/0118715206354755241220062707","url":null,"abstract":"<p><strong>Background: </strong>1,4-Naphthoquinone and its derivatives are recognized for their potent anticancer effects, establishing this pharmacophore as a key focus in cancer research. Their potential to modulate cellular pathways suggests they could be effective in developing new HuR inhibitors, targeting a protein crucial for regulating cancer-related gene expression. Compounds C1-C20 were designed by using Discovery Studio (DS) software.</p><p><strong>Methods: </strong>In this study, a systematic approach involves scaffold hopping followed by additional research such as molecular docking, ADMET, drug-likeness, toxicity prediction, molecular dynamic (MD) simulation, and binding free energy analysis was used to discover novel Human Antigen R (HuR) inhibitors.</p><p><strong>Results: </strong>In molecular docking, 1,4-Naphthoquinone derivatives showed better interactions with the HuR protein compared to that of the conventional HuR inhibitor MS-444. Among twenty 1,4-Naphthoquinone derivatives, most of the compounds showed favorable pharmacokinetic characteristics. In the toxicity prediction model, most of the designed compounds were neither mutagenic nor carcinogenic. According to MD simulation, C5 is more stable than MS-444.</p><p><strong>Conclusion: </strong>The designed 1,4-Naphthoquinone derivatives have been found to be crucial structural motifs for the discovery of novel HuR inhibitors, which was well supported by the in-silico screening and molecular modeling methods.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363583","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}