Anti-cancer agents in medicinal chemistry最新文献

{"title":"A Novel Effective Models for Identifying BRCA Patients and Optimizing Clinical Treatments.","authors":"Yi Luo, Li Liu, Zeyu Hou, Daigang Xiong, Rui Chen","doi":"10.2174/0118715206336019241119070155","DOIUrl":"https://doi.org/10.2174/0118715206336019241119070155","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to develop an effective model that identifies high-risk breast cancer (BRCA) patients and optimizes clinical treatments.</p><p><strong>Methods: </strong>This study includes five public datasets, TCGA-BRCA as the training dataset and other cohorts as the validation datasets. Machine learning algorithms for finding key tumor-associated immune gene pairs (TAIGPs). These TAIGPs were used to construct tumor-associated immune gene pair index (TAIGPI) by multivariate analysis and further validated on the validation datasets. In addition, the differences in clinical prognosis, biological characteristics, and treatment benefits between high and low TAIGPI groups were further analyzed.</p><p><strong>Results: </strong>The TAIGPI was established by 36 TAIGPs. Better clinical outcomes in the low TAIGPI patients, with consistent results, were also obtained in the validation datasets. The study showed that patients in the low TAIGPI group had a high infiltration of immune cells and low proliferative activity of tumor cells. In contrast, patients in the high TAIGPI group exhibited low infiltration of immune cells and high proliferative activity of tumor cells. In addition, patients in the low TAIGPI group are more likely to benefit from chemotherapy, adjuvant chemotherapy, or immunotherapy.</p><p><strong>Conclusions: </strong>The TAIGPI can be an effective predictive strategy for the clinical prognosis of breast cancer patients, providing new insights into personalized treatment options for breast cancer patients.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852217","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":"Discovery of a Novel Co-crystal of Chrysin and Oroxylin a with Anticancer Properties from Leaves of Oroxylum indicum.","authors":"Salam Asbin Singh, Asem Robinson Singh, Atom Rajiv Singh, Anoubam Sujita Devi, Minhaz Korimayum, Lisam Shanjukumar Singh","doi":"10.2174/0118715206364530241128044041","DOIUrl":"https://doi.org/10.2174/0118715206364530241128044041","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;As the number of new cancer cases increases every year, there is a necessity to develop new drugs for the treatment of different types of cancers. Plants' resources are considered to be huge reservoirs for therapeutic agents in nature. Among all the medicinal plants, Oroxylum indicum is one of the most widely used medicinal plants in India, China, and Southeast Asian countries. Combinatorial drug treatment, on the other hand, is favored over single drug treatment in order to target multiple biomolecular moieties that help in the growth and development of cancer. Therefore, combinatorial drug treatment using a co-crystal of multiple drugs gives researchers an idea of the development of a new type of drug for targeting multiple targets. In this study, a new co-crystal of chrysin and oroxylin A was isolated from the leaves of O. indicum, and its anticancer properties were studied in cervical cancer cells HeLa.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;This study was conducted with the aim of identifying new anticancer compounds from the leaves of Oroxylum indicum and studying the anticancer properties of the isolated compound.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;In this study, we elucidated the structure of a new co-crystal compound, which was isolated from the leaf extract of Oroxylum indicum. The apoptosis induction mechanism of the newly discovered co-crystal in HeLa cells was also studied.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A crystal compound from the chloroform extract of leaves of Oroxylum Indicum was isolated by solvent fractionation and chromatographic methods involving HPLC. The molecular structure of the isolated crystal was elucidated by Single Crystal-XRD, FT-IR analysis, and further determined by LC-MS. The antiproliferative activity was carried out using an MTT assay and fluorescence microscopy, and the mechanism of apoptosis was determined using Western blotting techniques.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The novel co-crystal consists of two active pharmaceutical ingredients (APIs) in a 1:1 ratio, i.e., oroxylin A and chrysin. The isolated new co-crystal induced death in HeLa cells with a very low IC50 value of 8.49μM. It induced caspase-dependent apoptosis in HeLa cells by activation of Caspase-3 through inhibition of ERKs and activation of p38 of MAPK cell signalling pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study presents the first report on the discovery of a naturally occurring co-crystal of chrysin and oroxylin A and the involvement of ERKs and p38 of MAPK pathways in the induction of apoptosis in HeLa cells by the co-crystal. Our study sheds light on the development of a co-crystal of chrysin and oroxylin A in a specific ratio of 1:1 for combination therapy of the two APIs. The purified co-crystal was found to be more efficient compared to the compounds present individually. Further analysis of the physiochemical properties and molecular mechanisms of the isolated co-crystal in different cancer cells is warr","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827218","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":"Emerging AXL Inhibitors in Oncology: Chemical and Biological Advances in Targeted Cancer Therapy.","authors":"Kamal Shah, Krishan Gopal, Shivendra Kumar, Sunam Saha","doi":"10.2174/0118715206351185241209053053","DOIUrl":"https://doi.org/10.2174/0118715206351185241209053053","url":null,"abstract":"<p><p>AXL, a receptor tyrosine kinase, has emerged as a critical player in tumorigenesis, metastasis, and resistance to conventional therapies. Its aberrant activation drives cell proliferation, survival, and angiogenesis, making it an attractive target for cancer treatment. In recent years, significant progress has been made in the development of AXL inhibitors. Chemical approaches have led to the discovery of small molecules that selectively bind to and inhibit AXL, disrupting its downstream signaling pathways. These inhibitors exhibit diverse structural features, including ATP-competitive and allosteric binding modes, offering potential advantages in terms of selectivity and potency. In addition to chemical approaches, biological strategies have also been explored to target AXL. These include the use of monoclonal antibodies, which can neutralize AXL ligands or induce receptor internalization and degradation. Furthermore, gene therapy techniques have been investigated to downregulate AXL expression or disrupt its signaling pathways. Despite these advancements, challenges remain in the development of AXL inhibitors. Selectivity is a critical concern, as AXL shares homology with other receptor tyrosine kinases. Drug resistance is another obstacle, as cancer cells can develop mechanisms to evade AXL inhibition. Furthermore, to address these challenges, combination therapies are being explored, such as combining AXL inhibitors with other targeted agents or conventional treatments. In conclusion, developing AXL inhibitors represents a promising avenue for improving cancer treatment outcomes. Continued research efforts are essential to overcome the existing challenges and translate these compounds into effective clinical therapies.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827219","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":"Capivasertib: First Approved AKT inhibitor for the Treatment of Patients with Breast Cancer.","authors":"Surya K DE","doi":"10.2174/0118715206360571241126080725","DOIUrl":"https://doi.org/10.2174/0118715206360571241126080725","url":null,"abstract":"<p><p>Breast cancer frequently occurs in women. Among the several types of breast cancers, almost 50% of breast cancers are caused by one or more gene mutations of the PI3K/mTOR/AKT pathway. Capivasertib, the first AKT inhibitor, was authorized by the US FDA on November 16, 2023.. It is used for the treatment of adult patients with hormone receptor-positive, human epidermal growth factor receptor 2 negative metastatic breast cancer with at least one alteration on PIK3CA/AKT1/PTEN. In this short perspective, Capivasertib's physicochemical properties, synthesis, mechanism of action, binding mode, pharmacokinetics, drug interaction studies, and treatment-emergent adverse events are discussed.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779400","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":"Anti-Inflammatory and Anti-proliferative Role of Essential Oil of Leaves of <i>Cleistocalyx operculatus</i> (Roxb.) Merr. & Perry.","authors":"Vivek Pandey, Sumnath Khanal, Nerina Shahi, Rupak Parajuli, Achyut Adhikari, Yuba Raj Pokharel","doi":"10.2174/0118715206304193240715043704","DOIUrl":"https://doi.org/10.2174/0118715206304193240715043704","url":null,"abstract":"<p><strong>Background: </strong>Phytochemicals have long remained an essential component of the traditional medicine system worldwide. Advancement of research in phytochemicals has led to the identification of novel constituents and metabolites from phytochemicals, performing various vital functions ranging from antimicrobial properties to anticarcinogenic roles. This plant is traditionally used by local people to manage inflammation. In this study, we aim to extract and chemically profile the essential oil from the leaves of Cleistocalyx operculatus (Roxb.) Merr. & Perry and study of the anti-inflammatory and anti-proliferative role of essential oil.</p><p><strong>Methods: </strong>The hydro distillation method was used for the extraction of essential oil, and the GC-MS was applied for the chemical profiling. The percentage of cell viability was calculated using a crystal violet assay, colony formation assay was performed using Semiquantitative PCR, Propodium iodite staining was used for cell death assay, and Western blotting was used to determine antibodies and proteins. Schrodinger 2015 software was used for molecular docking.</p><p><strong>Results: </strong>Myrcene, a monoterpene, constitutes 56% of the oil and could be attributed to its anti-inflammatory potential. Treatment of LPS-challenged mouse macrophages RAW264.7 cells with essential oil resulted in a decline in the inflammatory markers, such as IL-1β, TNFα, iNOS, COX-2, and NFκB. Further, essential oil inhibited cancer PC-3, A431, A549, and MCF-7 cell lines at concentrations lower than normal PNT2 and HEK-293 cell lines. This decline in proliferative potential can be attributed to a decline in anti-apoptotic proteins, such as procaspase 3 and PARP, an increase in CKIs, such as p21, and a decline in the Akt signaling responsible for survival.</p><p><strong>Conclusion: </strong>The essential oil of the plant Cleistocalyx operculatus may be a potential lead for anti-inflammatory and anti-proliferative function.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680595","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":"Amide Functionalized Novel Pyrrolo-pyrimidine Derivative as Anticancer Agents: Synthesis, Characterization and Molecular Docking Studies.","authors":"Praveen Kumar Bandaru, Satya Kameswara Rao N, Shyamala P","doi":"10.2174/0118715206333935241004070350","DOIUrl":"10.2174/0118715206333935241004070350","url":null,"abstract":"<p><strong>Background: </strong>The development of new therapies targeting crucial kinases involved in cancer progression is a promising area of research. Pyrazolo pyrimidine derivatives have emerged as potential candidates for this purpose.</p><p><strong>Objective: </strong>This study aims to synthesize pyrazolo pyrimidine derivatives (5a-5r), evaluate their molecular docking against key kinases, and assess their anticancer activity.</p><p><strong>Methods: </strong>The synthesis involved a multi-step procedure starting with the cyclization of 6-amino-2- methylpyrimidin-4(3H)-one (1) to form 2-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-4-ol (2). This was followed by chlorination to yield 4-chloro-2-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine (3) and nucleophilic substitution to produce 2-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-4-amine (4). The final derivatives (5a-5r) were synthesized through amide bond formation with various carboxylic acids using DCC and DMAP. Structural elucidation was confirmed via NMR, mass spectrometry, and HRMS. Molecular docking studies were conducted against Janus kinase 1 (JAK1), Janus kinase 2 (JAK2), and cyclin-dependent kinase 4 (CDK4). Anticancer activity was evaluated against MCF-7, SET-2, and HCT-116 cell lines.</p><p><strong>Results: </strong>Structural elucidation confirmed the successful synthesis of the derivatives. Molecular docking studies revealed promising binding affinities for selected derivatives, particularly those with heterocyclic substitutions. Anticancer activity evaluation showed diverse potency profiles, with several derivatives demonstrating IC50 values comparable to the reference drug, doxorubicin. Derivatives featuring nitro and heterocyclic moieties exhibited significant anticancer activity.</p><p><strong>Conclusion: </strong>The synthesized pyrazolo pyrimidine derivatives showed potential as lead compounds for further development due to their promising binding affinities and significant anticancer activity, particularly those with nitro and heterocyclic moieties.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590100","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":"Composition and Biological Activity of Flavonoid-containing Fractions of an Extract from Gratiola officinalis L.","authors":"Alexander Shirokov, Vyacheslav Grinev, Matvey Kanevskiy, Yulia Fedonenko, Larisa Matora, Natalya Polukonova, Dmitry Mudrak, Artyom Mylnikov, Anna Polukonova, Alla Bucharskaya, Nikita Navolokin, Galina Maslyakova","doi":"10.2174/0118715206323280241029215900","DOIUrl":"10.2174/0118715206323280241029215900","url":null,"abstract":"<p><strong>Introduction: </strong>Gratiola officinalis L. (hedge hyssop), a medicinal plant of the Scrophulariaceae family, has diuretic, purgative, and vermifuge properties. It is used as a herbal tea to treat chronic gastroenteritis, renal colic, jaundice, and intestinal worms. Previously, we have found that an extract from G. officinalis is nontoxic and has antitumor, antioxidant, antimicrobial, antiinflammatory, anticachexic, and other properties. Our aims in this study were to separate the G. officinalis extract into individual fractions, to identify the most biologically active fractions, and to examine the chemical composition of these fractions and their biological activity toward A498 renal carcinoma cells.</p><p><strong>Methods: </strong>The G. officinalis extract was fractionated by reversed-phase high-performance liquid chromatography, and each fraction was tested for antitumor activity. The active fractions were characterized by UV-visible electron spectral analysis, circular dichroism analysis, Fourier transform infrared spectroscopy, high-performance liquid chromatography, electrospray ionization tandem mass spectrometry, and nuclear magnetic resonance spectroscopy.</p><p><strong>Results: </strong>Two antitumor-active fractions of a flavonoid nature were isolated and chromatographically purified. On the basis of the nuclear magnetic resonance data, the aglycone fragment of the main component of one fraction was found to be structured as 2-(3,4-dimethoxyphenyl)-7-hydroxychroman-4-one, or 3',4'-dimethoxy-7- hydroxyflavanone.</p><p><strong>Conclusion: </strong>The antitumor effect of the most active fraction containing 7-O-glucoside of apigenin, glycoside 7,3'-di-O-luteolin and trace amounts of eupatilin against renal carcinoma A498 cells was manifested in its cytotoxic, cytostatic, apoptotic and autophagosomal activities. In addition, we found 3-(1-2)-glucoside of soyaspogenol B, which is a pentacyclic triterpenoid in the structure.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590104","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 of Chromene-linked Bis-indole Derivatives as Selective Tumor-associated Carbonic Anhydrase IX Inhibitors.","authors":"Priti Singh, Sridhar Goud Nerella, Baijayantimala Swain, Andrea Angeli, Samreen Kausar, Qasim Ullah, Claudiu T Supuran, Mohammed Arifuddin","doi":"10.2174/0118715206341087241029064945","DOIUrl":"https://doi.org/10.2174/0118715206341087241029064945","url":null,"abstract":"<p><strong>Background: </strong>Sulfonamide derivatives are well-reported hCA IX inhibitors; however, they inhibit all types of hCA without any selectivity, leading to severe adverse effects. Hence, developing a novel nonsulfonamide class of tumor-associated hCA IX inhibitors through non-classical inhibition may provide greater selectivity and better pharmacokinetics.</p><p><strong>Objective: </strong>The objective of this study was to develop non-sulfonamide derivatives as potential human carbonic anhydrase (hCA) inhibitors and develop a new series of chromene-linked bis-indole derivatives.</p><p><strong>Methods: </strong>We synthesized and characterized the chromene-linked bis-indole derivatives and further evaluated them against four hCA isoforms, i.e., hCA I, hCA II, hCA IX, and hCA XII, and determined the ADMET parameters by the In-silico method.</p><p><strong>Results: </strong>Most of the compounds showed significantly greater affinity and selectivity towards the tumorassociated hCA IX over other hCA isoforms within the lower micromolar to submicromolar range. In particular, the bromo-substituted bis-indole derivative 6t showed an excellent inhibition of hCA IX isoform with an affinity (Ki) of 2.61 μM. In contrast, the cyano group substituted bis-indole derivative 6s and also displayed a strong inhibition of hCA IX isoform with an affinity (Ki) of 2.73 μM. Many other potential candidates, including 6g, 6i, 6k, 6m, 6o, 6p, and 6r, showed higher affinity at tumor-associated hCA IX with lower than 10 μM compared to other hCA isoforms.</p><p><strong>Conclusion: </strong>Therefore, the chromene-linked bis-indole derivatives can serve as a novel non-sulfonamide class of tumor-associated hCA IX inhibitors.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581910","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 Review of Anticancer Potential of Conferone, Diversin and Ferutinin; Which One is Stronger for Cancer Therapy?","authors":"Fariborz Keshmirshekan, Seyed-Mahdi Mohamadi-Zarch, Seyyed Majid Bagheri","doi":"10.2174/0118715206328175241022081832","DOIUrl":"https://doi.org/10.2174/0118715206328175241022081832","url":null,"abstract":"<p><strong>Background: </strong>One of the growing diseases in today's human societies is cancer, which has become a major challenge, especially in industrialized and developing countries. Cancer treatments are diverse, but they usually use surgery, chemotherapy, and radiotherapy to improve patients. Existing drugs are usually expensive and, in some cases, are not effective due to drug resistance and side effects. Finding compounds of natural origin can be somewhat effective and useful in helping doctors to treat this disease. Ferula plants, which are traditionally used as spices or for medicinal purposes, can be a good source for finding anti-cancer compounds due to their various compounds, such as monoterpenes, sulfide compounds, and polyphenols. Several studies have shown that compounds found in Ferula plants have significant anticancer effects on various types of cancer cells.</p><p><strong>Objective: </strong>This article was compiled with the aim of collecting evidence and articles related to the anti-cancer effects of three compounds obtained from these plants, namely Conferone, Diversin, and Ferutinin.</p><p><strong>Methods: </strong>This review article was prepared by searching the terms Conferone, Diversin, Ferutinin and cancer and related information was collected through searching electronic databases such as ISI Web of Knowledge, PubMed and Google Scholar until the March of 2024.</p><p><strong>Conclusion: </strong>The results of this review showed that relatively comprehensive studies have been conducted in this field and these studies have shown that these compounds can be used in the design of future anticancer drugs. Among the examined compounds, conferone showed that it has the best effect on cancer cells.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557039","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":"Investigation of Apoptotic and Anticancer Effects of 2-substituted Benzothiazoles in Breast Cancer Cell Lines: EGFR Modulation and Mechanistic Insights.","authors":"Muhammed Mehdi Üremiş, Mustafa Ceylan, Yusuf Türköz","doi":"10.2174/0118715206335840241018053929","DOIUrl":"https://doi.org/10.2174/0118715206335840241018053929","url":null,"abstract":"<p><strong>Background and objective: </strong>Benzothiazole derivatives, a class of heterocyclic compounds, exhibited diverse biological activities influenced by substituents in the thiazole ring. This study aimed to synthesize these compounds with two functional groups to investigate their potential as anticancer agents, particularly against breast cancer. While previous research demonstrated the efficacy of 2-substituted benzothiazoles against glioma and cervical and pancreatic cancer cells, there is a gap in studies targeting breast cancer.</p><p><strong>Methods: </strong>The synthesized compounds were tested in vitro using MCF-7, MDA-MB-231, and MCF-10A cell lines, with Doxorubicin as the positive control. Various assays were conducted, including Annexin V/PI, cell cycle analysis, wound healing, and measurement of mitochondrial membrane potential. Protein expression of EGFR and transcription levels of apoptosis-related genes (Bax and Bcl-xL) and cancer progression-related genes (JAK, STAT3, ERK, AKT, mTOR) were analyzed. Additionally, the balance between antioxidants and oxidants was evaluated by measuring TAS and TOS levels.</p><p><strong>Results: </strong>Our findings revealed that benzothiazole compounds significantly inhibited breast cancer cell growth by reducing cell motility, disrupting mitochondrial membrane potential, and inducing cell cycle arrest in the sub-G1 phase. These compounds increased reactive oxygen species accumulation, leading to cell death. Furthermore, they decreased EGFR protein levels, increased Bax gene transcription, and downregulated the expression of genes such as JAK, STAT3, ERK, AKT, and mTOR.</p><p><strong>Conclusion: </strong>In conclusion, benzothiazole derivatives exhibited potent inhibitory effects on breast cancer in vitro by promoting apoptosis, downregulating EGFR activity, and modulating key signaling pathways, including JAK/STAT, ERK/MAPK, and PI3K/Akt/mTOR. These results highlighted the potential of benzothiazole derivatives as novel therapeutic agents for breast cancer treatment.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543224","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}