Anti-cancer agents in medicinal chemistry最新文献

{"title":"Arsenic Trioxide Suppresses Angiogenesis in Non-small Cell Lung Cancer <i>via</i> the Nrf2-IL-33 Signaling Pathway.","authors":"Mingdong Wang, Jizhong Yin, Qianyu Han, Bing Li, Xue-Wei Zhao, Lei Xue","doi":"10.2174/0118715206288348240420174853","DOIUrl":"10.2174/0118715206288348240420174853","url":null,"abstract":"<p><strong>Background: </strong>Non-Small Cell Lung Cancer (NSCLC) ranks as a leading cause of cancer-related mortality, necessitating the urgent search for cost-effective and efficient anti-NSCLC drugs. Our preliminary research has demonstrated that arsenic trioxide (ATO) significantly inhibits NSCLC angiogenesis, exerting anti-tumor effects. In conjunction with existing literature reports, the Nrf2-IL-33 pathway is emerging as a novel mechanism in NSCLC angiogenesis.</p><p><strong>Objective: </strong>This study aimed to elucidate whether ATO can inhibit NSCLC angiogenesis through the Nrf2-IL-33 pathway.</p><p><strong>Methods: </strong>Immunohistochemistry was employed to assess the expression of Nrf2, IL-33, and CD31 in tumor tissues from patients with NSCLC. DETA-NONOate was used as a nitric oxide (NO) donor to mimic high levels of NO in the tumor microenvironment. Western blot, quantitative real-time PCR, and enzyme-linked immunosorbent assay were utilized to evaluate the expression of Nrf2 and IL-33 in the NCI-H1299 cell line. Subcutaneous xenograft models were established in nude mice by implanting NCI-H1299 cells to assess the anti-tumor efficacy of ATO.</p><p><strong>Results: </strong>High expression levels of Nrf2 and IL-33 were observed in tumor samples from patients with NSCLC, and Nrf2 expression positively correlated with microvascular density in NSCLC. <i>In vitro</i>, NO (released from 1mM DETA-NONOate) promoted activation of the Nrf2-IL-33 signaling pathway in NCI-H1299 cells, which was reversed by ATO. Additionally, both Nrf2 deficiency and ATO treatment significantly attenuated NOinduced IL-33 expression. <i>In vivo</i>, both ATO and the Nrf2 inhibitor ML385 demonstrated significant inhibitory effects on angiogenesis tumor growth.</p><p><strong>Conclusion: </strong>Nrf2-IL-33 signaling is usually activated in NSCLC and positively correlates with tumor angiogenesis. ATO effectively disrupts the activation of the Nrf2-IL-33 pathway in NSCLC and thus inhibits angiogenesis, suggesting its potential as an anti-angiogenic agent for use in the treatment of NSCLC.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282798","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":"Hyperoxic-hypoxic Paradox: Breast Cancer Microenvironment and an Innovative Treatment Strategy.","authors":"Suman Kumar Ray, Sukhes Mukherjee","doi":"10.2174/0118715206290816240220062545","DOIUrl":"10.2174/0118715206290816240220062545","url":null,"abstract":"<p><p>A small therapeutic range of oxygen is required for effective metabolism. As a result, hypoxia (low oxygen concentration) is one of the most potent inducers of gene expression, metabolic alterations, and regenerative processes, such as angiogenesis, stem cell proliferation, migration, and differentiation. The cellular response is controlled by sensing the increased oxygen levels (hyperoxia) or hypoxia via specific chemoreceptor cells. Surprisingly, changes in free oxygen concentration instead of absolute oxygen levels may be regarded as a deficiency of oxygen at the cellular level. Recurrent intermittent hyperoxia may trigger many mediators of cellular pathways typically generated during hypoxia. The dilemma of hyperoxic-hypoxic conditions is known as the hyperoxic-hypoxic paradox. According to the latest data, the hypoxic microenvironment, crucial during cancer formation, has been demonstrated to play a key role in regulating breast cancer growth and metastasis. Hypoxic circumstances cause breast cancer cells to respond in a variety of ways. Transcription factors are identified as hypoxia-inducible factors (HIFs) that have been suggested to be a factor in the pathobiology of breast cancer and a possible therapeutic target, driving the cellular response to hypoxia. Breast cancer has a dismal prognosis due to a high level of resistance to practically all well-known cancer management that has been related to hypoxia-based interactions between tumor cells and the stromal milieu. We attempt to review the enigma by exploring the starring roles of HIFs in breast cancer, the HIF paradox, and the hyperoxic-hypoxic enigma.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982200","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":"Bee Venom Toxic Effect on MDA-MB-231 Breast Cancer Cells and <i>Caenorhabditis Elegans</i>.","authors":"Yáskara Veruska Ribeiro Barros, Amanda Onduras de Andrade, Larissa Pereira Dantas da Silva, Lucas Aleixo Leal Pedroza, Iverson Conrado Bezerra, Iago Dillion Lima Cavalcanti, Mariane Cajuba de Britto Lira Nogueira, Kristiana Cerqueira Mousinho, Angelo Roberto Antoniolli, Luiz Carlos Alves, José Luiz de Lima Filho, Alexandre Varão Moura, Álex Aparecido Rosini Silva, Andréia de Melo Porcari, Priscila Gubert","doi":"10.2174/0118715206291634240312062957","DOIUrl":"10.2174/0118715206291634240312062957","url":null,"abstract":"<p><strong>Introduction: </strong>Bee venom has therapeutics and pharmacological properties. Further toxicological studies on animal models are necessary due to the severe allergic reactions caused by this product.</p><p><strong>Method: </strong>Here, <i>Caenorhabditis elegans</i> was used as an <i>in vivo</i> toxicity model, while breast cancer cells were used to evaluate the pharmacological benefits. The bee venom utilized in this research was collected from <i>Apis mellifera</i> species found in Northeast Brazil. The cytotoxicity caused by bee venom was measured by MTT assay on MDA-MB-231 and J774 A.1 cells during 24 - 72 hours of exposure. <i>C. elegans</i> at the L4 larval stage were exposed for three hours to M9 buffer or bee venom. Survival, behavioral parameters, reproduction, DAF-16 transcription factor translocation, the expression of superoxide dismutase (SOD), and metabolomics were analyzed. Bee venom suppressed the growth of MDA-MB-231 cancer cells and exhibited cytotoxic effects on macrophages. Also, decreased <i>C. elegans</i> survival impacted its behaviors by decreasing <i>C. elegans</i> feeding behavior, movement, and reproduction.</p><p><strong>Results: </strong>Bee venom did not increase the expression of SOD-3, but it enhanced DAF-16 translocation from the cytoplasm to the nucleus. <i>C. elegans</i> metabolites differed after bee venom exposure, primarily related to aminoacyl- tRNA biosynthesis, glycine, serine and threonine metabolism, and sphingolipid and purine metabolic pathways. Our findings indicate that exposure to bee venom resulted in harmful effects on the cells and animal models examined.</p><p><strong>Conclusion: </strong>Thus, due to its potential toxic effect and induction of allergic reactions, using bee venom as a therapeutic approach has been limited. The development of controlled-release drug strategies to improve this natural product's efficacy and safety should be intensified.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157386","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-lung Cancer Activity of Synthesized Substituted 1,4-Benzothiazines: An Insight from Molecular Docking and Experimental Studies.","authors":"Andleeb Amin, Zubaid-Ul- Khazir, Arfa Ji, Basharat Ahmad Bhat, Dar Murtaza, Aaqib A Hurrah, Imtiyaz A Bhat, Shaheena Parveen, Syed Nisar, Praveen Kumar Sharma","doi":"10.2174/0118715206276737231103114924","DOIUrl":"10.2174/0118715206276737231103114924","url":null,"abstract":"<p><strong>Background: </strong>Thiazine, a 6-membered distinctive heterocyclic motif with sulfur and nitrogen atoms, is one of the heterocyclic compounds that functions as a core scaffold in a number of medicinally significant molecules. Small thiazine-based compounds may operate simultaneously on numerous therapeutic targets and by employing a variety of methods to halt the development, proliferation, and vasculature of cancer cells. We have, herein, reported a series of substituted 1,4 benzothiazines as potential anticancer agents for the treatment of lung cancer.</p><p><strong>Methods: </strong>In order to synthesize 2,3-disubstituted-1,4 benzothiazines in good yield, a facile green approach for the oxidative cycloaddition of 2-amino benzenethiol and 1,3-dicarbonyls employing a catalytic amount of ceric ammonium nitrate has been devised. All the molecules have been characterized by spectral analysis and tested for anticancer activity against the A-549 lung cancer cell line using various functional assays. Further in silico screening of compound 3c against six crucial inflammatory molecular targets, such as Il1-α (PDB ID: 5UC6), Il1- β (PDB ID: 6Y8I), Il6 (PDB ID: 1P9M), vimentin (PDB ID: 3TRT), COX-2 (PDB ID: 5KIR), Il8 (PDB ID: 5D14), and TNF-α (PDB ID: 2AZ5), was done using AutoDock tool.</p><p><strong>Results: </strong>Among the synthesized compounds, propyl 3-methyl-3,4-dihydro-2H-benzo[b][1,4]thiazine-2- carboxylate (3c) was found to be most active based on cell viability assays using A-549 lung cancer cell line and was found to effectively downregulate various pro-inflammatory genes, like Il1-α, Il1-β, Il6, vimentin, COX-2, Il8, and TNF-α <i>in vitro</i>. The ability of the molecule to effectively suppress the proliferation and migration of lung cancer cells <i>in vitro</i> has been further demonstrated by the colony formation unit assay and wound healing assay. Molecular docking analysis showed the maximal binding affinity (- 7.54 kcal/mol) to be exhibited by compound 3c against IL8.</p><p><strong>Conclusion: </strong>A green unconventional route for the synthesis of 2,3-disubstituted-1,4 benzothiazines has been developed. All the molecules were screened for their activity against lung cancer and the data suggested that the presence of an additional unbranched alkyl group attached to the thiazine ring increased their activity. Also, <i>in vitro</i> and <i>in silico</i> modeling confirmed the anti-cancer efficiency of compound 3c, encouraging the exploration of such small molecules against cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152290","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":"Ginsenoside Rb1 Inhibits the Proliferation of Lung Cancer Cells by Inducing the Mitochondrial-mediated Apoptosis Pathway.","authors":"Lin Feng, Xinze Liu, Kaijing Sun, Ying Sun, Wei Wu, Changbao Chen, Xin Jin, Xilin Wan","doi":"10.2174/0118715206299212240304142047","DOIUrl":"10.2174/0118715206299212240304142047","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is one of the more common malignant tumors posing a great threat to human life, and it is very urgent to find safe and effective therapeutic drugs. The antitumor effect of ginsenosides has been reported to be a treatment with a strong effect and a high safety profile.</p><p><strong>Objective: </strong>This paper aimed to investigate the inhibitory effect of ginsenoside Rb1 on 95D and NCI-H460 lung cancer cells and its pathway to promote apoptosis.</p><p><strong>Methods: </strong>We performed the CCK-8 assay, fluorescence staining assay, flow cytometry, scratch healing assay, and Transwell assay to detect the effects of different concentrations of ginsenoside Rb1 on the antitumor activity of 95D and NCI-H460 cells and Western Blot detected the mechanism of antitumor effect.</p><p><strong>Results: </strong>Ginsenoside Rb1 treatment significantly increased the inhibition and apoptosis rates of 95D and NCIH460 cells and inhibited the cell cycle transition from S phase to G2/M. Rb1 induces apoptosis by altering the levels of P53, Bax, Cyto-c, Caspase-8, Caspase-3, Cleaved Caspase-3, Bcl-2, MMP-2, and MMP-9 proteins and activating the external apoptotic pathway.</p><p><strong>Conclusion: </strong>Ginsenoside Rb1 inhibits proliferation and migration and induces apoptosis of 95D and NCI-H460 lung cancer cells by regulating the mitochondrial apoptotic pathway to achieve antitumor activity.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093359","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":"Preparation, Characterization, and Anticancer Activity Assessment of Chitosan/TPP Nanoparticles Loaded with <i>Echis carinatus</i> Venom.","authors":"Maral Mahboubi Kancha, Mohsen Mehrabi, Fatemeh Sadat Bitaraf, Hamid Vahedi, Morteza Alizadeh, Andreas Bernkop-Schnürch","doi":"10.2174/0118715206279731231129105221","DOIUrl":"10.2174/0118715206279731231129105221","url":null,"abstract":"<p><strong>Aims and background: </strong><i>Echis carinatus</i> venom is a toxic substance naturally produced by special glands in this snake species. Alongside various toxic properties, this venom has been used for its therapeutic effects, which are applicable in treating various cancers (liver, breast, <i>etc.</i>).</p><p><strong>Objective: </strong>Nanotechnology-based drug delivery systems are suitable for protecting <i>Echis carinatus</i> venom against destruction and unwanted absorption. They can manage its controlled transfer and absorption, significantly reducing side effects.</p><p><strong>Methods: </strong>In the present study, chitosan nanoparticles were prepared using the ionotropic gelation method with emulsion cross-linking. The venom's encapsulation efficiency, loading capacity, and release rate were calculated at certain time points. Moreover, the nanoparticles' optimal formulation and cytotoxic effects were determined using the MTT assay.</p><p><strong>Results: </strong>The optimized nanoparticle formulation increases cell death induction in various cancerous cell lines. Moreover, chitosan nanoparticles loaded with <i>Echis carinatus</i> venom had a significant rate of cytotoxicity against cancer cells.</p><p><strong>Conclusion: </strong>It is proposed that this formulation may act as a suitable candidate for more extensive assessments of cancer treatment using nanotechnology-based drug delivery systems.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511527","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 and Biological Evaluation of Thiazole-based Fibroblast Growth Factor Receptor-1 Inhibitors.","authors":"Mohammad A Khanfar, Ibrahim M Salman, Omar Z Ameer","doi":"10.2174/1871520622666220905141248","DOIUrl":"10.2174/1871520622666220905141248","url":null,"abstract":"<p><strong>Background: </strong>The Fibroblast Growth Factor Receptor-1 (FGFR-1) is a tyrosine kinase and a validated target for the treatment of different cancer types.</p><p><strong>Objective: </strong>Design and synthesis of novel thiazole-based analogues of anticancer agents.</p><p><strong>Methods: </strong>Series of 2-aryl-5-methylthiazole analogues linked to structurally variable basic heads were synthesized as novel anticancer agents. Developed compounds were tested for their cytotoxic activities against several cancer cell lines.</p><p><strong>Results: </strong>Many analogues exhibited strong antiproliferative activities against breast cancer cell lines, with higher potency towards the highly metastatic form (MDA-MB-231). Pharmacophoric profiling using an in-house pharmacophore database identified FGFR-1 as a molecular target of active analogues. Synthesized compounds were bioassayed for their FGFR-1 inhibitory activities and many hits exhibited IC50 values in the low micromolar to nanomolar range.</p><p><strong>Conclusion: </strong>The 2-aryl-5-methylthiazole linked to a basic head is a novel chemical scaffold of ATP-competitive inhibitor of FGFR-1 with potential therapeutic activities against different types of cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40352111","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 and Molecular Dynamic Simulation of Novel Cationic and Non-cationic Pyrimidine Derivatives as Potential G-quadruplex-ligands.","authors":"Hoda Atapour-Mashhad, Mohammad Soukhtanloo, Shiva Golmohammadzadeh, Jamshidkhan Chamani, Mojgan Nejabat, Farzin Hadizadeh","doi":"10.2174/0118715206291797240523112439","DOIUrl":"10.2174/0118715206291797240523112439","url":null,"abstract":"<p><strong>Background: </strong>Drug resistance has been a problem in cancer chemotherapy, which often causes shortterm effectiveness. Further, the literature indicates that telomere G-quadruplex could be a promising anti-cancer target.</p><p><strong>Objective: </strong>We synthesized and characterized two new pyrimidine derivatives as ligands for G-quadruplex DNA.</p><p><strong>Methods: </strong>The interaction of novel non-cationic and cationic pyrimidine derivatives (3a, b) with G-quadruplex DNA (1k8p and 3qsc) was explored by circular dichroism (CD) and ultraviolet-visible spectroscopy and polyacrylamide gel electrophoresis (PAGE) methods. The antiproliferative activity of desired compounds was evaluated by the MTT assay. Apoptosis induction was assessed by Propidium iodide (P.I.) staining and flow cytometry. Computational molecular modeling (CMM) and molecular dynamics simulation (MD) were studied on the complexes of 1k8p and 3qsc with the compounds. The van der Waals, electrostatic, polar solvation, solventaccessible surface area (SASA), and binding energies were calculated and analyzed.</p><p><strong>Results: </strong>The experimental results confirmed that both compounds 3a and 3b interacted with 1k8p and 3qsc and exerted cytotoxic and proapoptotic effects on cancer cells. The number of hydrogen bonds and the RMSD values increased in the presence of the ligands, indicating stronger binding and suggesting increased structural dynamics. The electrostatic contribution to binding energy was higher for the cationic pyrimidine 3b, indicating more negative binding energies.</p><p><strong>Conclusion: </strong>Both experimental and MD results confirmed that 3b was more prone to form a complex with DNA G-quadruplex (1k8p and 3qsc), inhibit cell growth, and induce apoptosis, compared to the non-cationic pyrimidine 3a.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260405","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":"Antitumoral Potential of Artepillin C, a Compound Derived from Brazilian Propolis, against Breast Cancer Cell Lines.","authors":"Lyvia Eloiza de Freitas Meirelles, Analine Rosa Barquez de Assis Carvalho, Gabrielle Marconi Zago Ferreira Damke, Raquel Pantarotto Souza, Edilson Damke, Patrícia de Souza Bonfim-Mendonça, Djaceli Sampaio de Oliveira Dembogurski, Denise Brentan da Silva, Marcia Edilaine Lopes Consolaro, Vania Ramos Sela da Silva","doi":"10.2174/0118715206270534231103074433","DOIUrl":"10.2174/0118715206270534231103074433","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most commonly diagnosed cancer among women worldwide with limited treatment options. Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is one of the main constituents of Brazilian propolis presenting different activities, including antitumoral effects against various types of cancer.</p><p><strong>Objective: </strong>We evaluated the antitumoral potential and mechanisms of action of artepillin C against two distinct human breast cancer cell lines, MCF-7 and MDA-MB-231, to explore a new therapeutic candidate.</p><p><strong>Methods: </strong>Cell viability was assessed by MTT assay and the long-term cytotoxicity was performed by clonogenic assay. The morphological changes were observed by light microscopy, analysis of cell death pathway by Annexin V FITC/propidium iodide (PI), lactate dehydrogenase (LDH) by colorimetry, DNA fragmentation by agarose gel and senescence by β-galactosidase. Detection of total reactive oxygen species (ROS) by fluorescence microscopy and determination of mitochondrial transmembrane potential by flow cytometry were also performed.</p><p><strong>Results: </strong>Artepillin C presented a strong and dose-time-dependent cytotoxic effect on MCF-7 and MDA-MB-231 cell lines, with cytotoxicity more evident in MCF-7. In both cancer cell lines, the clonogenic potential was significantly reduced and the morphology of the cells was changed. The treatment also induced death by necrosis and late apoptosis in MCF-7 and MDA-MB-231 and induced cell senescence in MCF-7. Also, artepillin C increased total ROS in both cancer cells and decreased mitochondrial membrane potential in MDA-MB-231 cells.</p><p><strong>Conclusion: </strong>Artepillin C presented antitumoral potential in two human breast cancer cell lines, MCF-7, and MDA-MB-231, suggesting a new promising option for the treatment and/or chemopreventive strategy for breast cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152291","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":"Green Synthesis of a Novel Phytoalexin Derivative: <i>In Silico</i> Profiling, Apoptotic Induction, and Antiproliferative Activity against MCF-7 cells - From Vineyards to Potent Anticancer Drug Molecule.","authors":"Lairikyengbam Deepti Roy, Jyotsna Kumar","doi":"10.2174/0118715206277144231031071220","DOIUrl":"10.2174/0118715206277144231031071220","url":null,"abstract":"<p><strong>Background: </strong>Resveratrol's structural similarity to commercialized anti-breast cancer medications such as Tamoxifen underlines its potential as a promising option for developing successful anti-breast cancer drugs. However, the pharmacokinetic issues associated with resveratrol, such as its low bioavailability, have piqued the attention of researchers in developing novel derivatives.</p><p><strong>Methods: </strong>A novel phytoalexin derivative, RsvD1, was successfully synthesized using resveratrol extracted from green grape peels as a precursor to investigate its anti-breast cancer efficacy on Estrogen receptor (ER) positive and negative breast cancer cells.</p><p><strong>Results: </strong>The comparative analysis revealed that RsvD1 exhibited remarkable radical scavenging ability (IC₅₀ = 2.21 μg/mL), surpassing the control, Trolox (IC₅₀ = 6.3 μg/mL). Furthermore, RsvD1 demonstrated enhanced and selective antiproliferative activity against ER-positive MCF-7 cells (IC₅₀ = 20.09 μg/mL) compared to resveratrol, the parent molecule (IC₅₀ = 30.90 μg/mL). Further investigations unveiled that RsvD1 induced apoptosis and DNA damage in MCF-7 cells, leading to cell cycle arrest at the G₀/G₁ phase after 24 hours of incubation. RTqPCR gene expression analysis indicated that RsvD1 down-regulated the CAXII (ER-dependent) genes. <i>In silico</i> predictions demonstrated that RsvD1 possesses promising potential as a drug candidate due to its drug-like characteristics and favourable ADMET profile. Moreover, molecular docking studies provided insights into the theoretical binding mode between RsvD1 and ERα protein.</p><p><strong>Conclusion: </strong>The study highlights the therapeutic potential of the synthesized resveratrol derivative, RsvD1, positioning it as a promising scaffold for developing novel analogues with improved therapeutic properties and selectivity, specifically targeting ER+ breast cancer cells. Moreover, the compound's non-cytotoxic yet antiproliferative properties, coupled with its capability to induce programmed cell death and cell cycle arrest, enhance its potential as a highly effective drug candidate. As a result, this paves a promising path for the development of innovative and selective inhibitors targeting ER+ breast cancer with enhanced efficacy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477290","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}