Anti-cancer agents in medicinal chemistry最新文献

{"title":"Liposomal Nano-Based Drug Delivery Systems for Breast Cancer Therapy: Recent Advances and Progresses.","authors":"Mostafa Yazdan, Seyed Morteza Naghib, M R Mozafari","doi":"10.2174/0118715206293653240322041047","DOIUrl":"10.2174/0118715206293653240322041047","url":null,"abstract":"<p><p>Breast cancer is a highly prevalent disease on a global scale, with a 30% incidence rate among women and a 14% mortality rate. Developing countries bear a disproportionate share of the disease burden, while countries with greater technological advancements exhibit a higher incidence. A mere 7% of women under the age of 40 are diagnosed with breast cancer, and the prevalence of this ailment is significantly diminished among those aged 35 and younger. Chemotherapy, radiation therapy, and surgical intervention comprise the treatment protocol. However, the ongoing quest for a definitive cure for breast cancer continues. The propensity for cancer stem cells to metastasize and resistance to treatment constitute their Achilles' heel. The advancement of drug delivery techniques that target cancer cells specifically holds significant promise in terms of facilitating timely detection and effective intervention. Novel approaches to pharmaceutical delivery, including nanostructures and liposomes, may bring about substantial changes in the way breast cancer is managed. These systems offer a multitude of advantages, such as heightened bioavailability, enhanced solubility, targeted tumor destruction, and diminished adverse effects. The application of nano-drug delivery systems to administer anti-breast cancer medications is a significant subject of research. This article delves into the domain of breast cancer, conventional treatment methods, the incorporation of nanotechnology into managerial tactics, and strategic approaches aimed at tackling the disease at its core.</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":"140288070","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":"Combination of Ethacrynic Acid and ATRA Triggers Differentiation and/or Apoptosis of Acute Myeloid Leukemia Cells through ROS.","authors":"Lu Li, Hui-Min Xi, Hao Lu, Xun Cai","doi":"10.2174/0118715206273000231211092743","DOIUrl":"10.2174/0118715206273000231211092743","url":null,"abstract":"<p><strong>Background and objective: </strong>All-trans retinoic acid (ATRA), an effective differentiation inducer, has been applied clinically to treat acute promyelocytic leukemia (APL). Unfortunately, it is not as potent in other kinds of acute myeloid leukemia (AML). Ethacrynic acid (EA), a classical powerful diuretic, can increase reactive oxygen species (ROS) contents, which can assist ATRA in inducing differentiation in AML cells. Here, we investigated the effect of EA combined with ATRA (EA+RA) on some AML cells except APL.</p><p><strong>Methods: </strong>Apoptosis and differentiation were determined by morphology, cell viability, Annexin-V assay and CD11c expression. Western blot analysis and the detection of ROS and mitochondrial transmembrane potentials (MMP) were used to investigate the mechanisms.</p><p><strong>Results: </strong>AML cells exhibited differentiation and/or apoptosis after EA+RA treatment. EA+RA increased the intracellular ROS contents. EA+RA-induced apoptosis was accompanied by MMP attenuation and caspase-3/7 activation. EA+RA-induced differentiation was along with MEK/ERK and Akt activation and increased expression of PU.1, CCAAT/enhancer-binding protein β (C/EBPβ) and C/EBPε. N-acetyl-L-cysteine (NAC), an antioxidant, thoroughly reduced EA+RA-increased ROS, and also inhibited MMP attenuation, the activation of caspase- 3/7, MEK/ERK and Akt pathways, the elevation of PU.1 and C/EBPs, and apoptosis and differentiation. However, MEK or PI3K specific inhibitors only suppressed EA+RA-triggered differentiation and the elevation of PU.1 and C/EBPs, but not ROS levels.</p><p><strong>Conclusion: </strong>EA+RA induced cell apoptosis through ROS dependent MMP attenuation and caspase 3/7 activation while inducing differentiation by ROS-MEK/ERK-PU.1/C/EBPs and ROS-Akt-PU.1/C/EBPs pathways. In summary, it may provide innovative ATRA-based combination therapy strategies for AML patients <i>via</i> ROS.</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":"139416153","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":"Design, Synthesis and Anti-cancer Evaluation of Nitrogen-containing Derivatives of 30-Carboxyl of Gambogic Acid.","authors":"Hong Li, Huiping Lin, Jiajun Li, Kaixin Chen, Zanhong Chen, Jianye Zhang, Yan Huang, Xin Zhao, Huihui Ti, Yiwen Tao","doi":"10.2174/0118715206279725231208065031","DOIUrl":"10.2174/0118715206279725231208065031","url":null,"abstract":"<p><strong>Background: </strong>Gambogic acid (GA) is a natural product from the resin of the Garcinia species, which showed significant activity in the induction of apoptosis. .t can be one promising lead compound for the design and synthesis of new anticancer drugs.</p><p><strong>Objective: </strong>The objective of the current study is to design novel nitrogen-contained GA derivatives with better anti-cancer activities and study the effect of the introduction of different nitrogen-contained groups on the activity of GA.</p><p><strong>Methods: </strong>The designed 15 derivatives were synthesized via esterification or amidation of 30-carboxylate. The synthetic compounds were characterized <i>via</i> different spectroscopic techniques, including X-ray single crystal diffraction, MS and NMR. The cytotoxic activity of the designed derivatives was evaluated <i>in vitro</i> against A549, HepG-2, and MCF-7 cell lines using methyl thiazolyl tetrazolium (MTT) test.</p><p><strong>Results: </strong>15 nitrogen-contained GA derivatives were successfully synthesized and established. Based on the IC₅₀ values, compounds 9, 10, 11 and 13 showed stronger inhibitory effects on A549, HepG-2, MCF-7 cell lines than GA, while 9 is the most active compound with IC₅₀ value of 0.64-1.49 μM. Most derivatives of GA with esterification of C-30 including cyano-benzene ring were generally weaker than those of pyrimidinyl-substituted derivatives. In addition, length of alkyl linkers between C-30 of GA and nitrogen-contained group produced different effects on A549, HepG-2 and MCF-7 cell lines.</p><p><strong>Conclusion: </strong>The structure-activity relationship results show that aromatic substituent and linker length play important roles to improve the anticancer activities, while compound 9 with pyrimidine substituent and C-C-C linkers is the most active derivative against tested cell lines, and is a promising anti-cancer agent for further development.</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":"139416155","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":"Design, Synthesis, <i>In vitro</i> and <i>In vivo</i> Evaluation of New Imidazo[1,2-<i>a</i>]pyridine Derivatives as Cyclooxygenase-2 Inhibitors.","authors":"Nahid Ahmadi, Mona Khoramjouy, Mahsa Azami Movahed, Salimeh Amidi, Mehrdad Faizi, Afshin Zarghi","doi":"10.2174/0118715206269563231220104846","DOIUrl":"10.2174/0118715206269563231220104846","url":null,"abstract":"<p><strong>Background: </strong>Cyclooxygenase-2 (COX-2), the key enzyme in the arachidonic acid conversion to prostaglandins, is one of the enzymes associated with different pathophysiological conditions, such as inflammation, cancers, Alzheimer's, and Parkinson's disease. Therefore, COX-2 inhibitors have emerged as potential therapeutic agents in these diseases.</p><p><strong>Objective: </strong>The objective of this study was to design and synthesize novel imidazo[1,2-a]pyridine derivatives utilizing rational design methods with the specific aim of developing new potent COX-2 inhibitors. Additionally, we sought to investigate the biological activities of these compounds, focusing on their COX-2 inhibitory effects, analgesic activity, and antiplatelet potential. We aimed to contribute to the development of selective COX-2 inhibitors with enhanced therapeutic benefits.</p><p><strong>Methods: </strong>Docking investigations were carried out using AutoDock Vina software to analyze the interaction of designed compounds. A total of 15 synthesized derivatives were obtained through a series of five reaction steps. The COX-2 inhibitory activities were assessed using the fluorescent Cayman kit, while analgesic effects were determined through writing tests, and Born's method was employed to evaluate antiplatelet activities.</p><p><strong>Results: </strong>The findings indicated that the majority of the tested compounds exhibited significant and specific inhibitory effects on COX-2, with a selectivity index ranging from 51.3 to 897.1 and IC₅₀ values of 0.13 to 0.05 μM. Among the studied compounds, derivatives 5e, 5f, and 5j demonstrated the highest potency with IC₅₀ value of 0.05 μM, while compound 5i exhibited the highest selectivity with a selectivity index of 897.19. <i>In vivo</i> analgesic activity of the most potent COX-2 inhibitors revealed that 3-(4-chlorophenoxy)-2-[4-(methylsulfonyl) phenyl] imidazo[1,2-a]pyridine (5j) possessed the most notable analgesic activity with ED₅₀ value of 12.38 mg/kg. Moreover, evaluating the antiplatelet activity showed compound 5a as the most potent for inhibiting arachidonic acidinduced platelet aggregation. In molecular modeling studies, methylsulfonyl pharmacophore was found to be inserted in the secondary pocket of the COX-2 active site, where it formed hydrogen bonds with Arg-513 and His-90.</p><p><strong>Conclusion: </strong>The majority of the compounds examined demonstrated selectivity and potency as inhibitors of COX-2. Furthermore, the analgesic effects observed of potent compounds can be attributed to the inhibition of the cyclooxygenase enzyme.</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":"139563343","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 Comprehensive Review on Nanoparticles as a Targeted Delivery System for the Treatment of Lung Cancer.","authors":"Twinkle Gupta, Avinash Varanwal, Priyanshu Nema, Sakshi Soni, Arun Kumar Iyer, Ratnesh Das, Vandana Soni, Sushil Kumar Kashaw","doi":"10.2174/0118715206257442231109202235","DOIUrl":"10.2174/0118715206257442231109202235","url":null,"abstract":"<p><p>The second most common type of cancer is lung cancer, impacting the human population. Lung cancer is treated with a number of surgical and non-surgical therapies, including radiation, chemotherapy, and photodynamic treatment. However, the bulk of these procedures are costly, difficult, and hostile to patients. Chemotherapy is distinguished by inadequate tumour targeting, low drug solubility, and insufficient drug transport to the tumour site. In order to deal with the issues related to chemotherapy, extensive efforts are underway to develop and investigate various types of nanoparticles, both organic and inorganic, for the treatment of lung cancer. The subject of this review is the advancements in research pertaining to active targeted lung cancer nano-drug delivery systems treatment, with a specific emphasis on receptors or targets. The findings of this study are expected to assist biomedical researchers in utilizing nanoparticles (NPs) as innovative tools for lung cancer treatment, offering new methods for delivering drugs and reliable solid ligands.</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":"138443586","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":"Coumarin-derived Hydroxamic Acids as Histone Deacetylase Inhibitors: A Review of Anti-cancer Activities.","authors":"Nguyen Quang Khai, Tran Khac Vu","doi":"10.2174/0118715206272112231102063919","DOIUrl":"10.2174/0118715206272112231102063919","url":null,"abstract":"<p><p>Since coumarin and hydroxamic acid compounds are well-known in medicinal chemistry, a variety of their derivatives have been highlighted due to their potential uses for plentiful treatments. Different compounds of their derivatives acting through diverse activities, such as anti-tumor, anti-cancer, anti-inflammation, and histone deacetylase inhibition, have been comprehensively investigated by many researchers over the years. This present review provides the latest literature and knowledge on hydroxamic acids derived from coumarin. Overall, some recent advancements in biological activities of hybrid derivatives of hydroxamic acids containing coumarin moieties in medicinal chemistry are discussed.</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":"92152293","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":"Identification of Novel EGFR Inhibitors for the Targeted Therapy of Colorectal Cancer Using Pharmacophore Modelling, Docking, Molecular Dynamic Simulation and Biological Activity Prediction.","authors":"Amrutha Krishnan K, Sudha George Valavi, Amitha Joy","doi":"10.2174/0118715206275566231206094645","DOIUrl":"10.2174/0118715206275566231206094645","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is considered the second deadliest cancer in the world. One of the reasons for the occurrence of this cancer is the deregulation of the Epidermal Growth Factor Receptor (EGFR), which plays a critical role in regulating cell division, persistence, differentiation, and migration. The overexpression of the EGFR protein leads to its dysregulation and causes CRC.</p><p><strong>Objectives: </strong>Hence, this work aims to identify and validate novel EGFR inhibitors for the treatment of colorectal cancer employing various computer aided techniques such as pharmacophore modeling, docking, molecular dynamic simulation and Quantitative Structure-Activity Relationship (QSAR) analysis.</p><p><strong>Methods: </strong>In this work, a shared-featured ligand-based pharmacophore model was generated using the known inhibitors of EGFR. The best model was validated and screened against ZincPharmer and Maybridge databases, and 143 hits were obtained. Pharmacokinetic and toxicological properties of these hits were studied, and the acceptable ligands were docked against EGFR. The best five protein-ligand complexes with binding energy less than -5 kcal/mol were selected. The molecular dynamic simulation studies of these complexes were conducted for 100 nanoseconds (ns), and the results were analyzed. The biological activity of this ligand was calculated using QSAR analysis.</p><p><strong>Results: </strong>The best complex with Root Mean Square Deviation (RMSD) 3.429 Å and Radius of Gyration (RoG) 20.181 Å was selected. The Root Mean Square Fluctuations (RMSF) results were also found to be satisfactory. The biological activity of this ligand was found to be 1.38 μM.</p><p><strong>Conclusion: </strong>This work hereby proposes the ligand 2-((1,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)oxy)-N- (1H-indol-4-yl)acetamide as a potential EGFR inhibitor for the treatment of colorectal cancer. The wet lab analysis must be conducted, however, to confirm this hypothesis.</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":"139085571","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":"<i>Antheraea proylei</i> J. Sericin Induces Apoptosis in a Caspase-dependent Manner in A549 and HeLa Cells.","authors":"Potsangbam Jolly Devi, Asem Robinson Singh, Naorem Tarundas Singh, Laishram Rupachandra Singh, Sanjenbam Kunjeshwori Devi, Lisam Shanjukumar Singh","doi":"10.2174/1871520623666230329123437","DOIUrl":"10.2174/1871520623666230329123437","url":null,"abstract":"<p><strong>Background: </strong>In spite of much progress in cancer, the global cancer burden is still significant and increasing. Sericin, an adhesive protein of silk cocoons, has been shown to be a potential protein in various biomedical applications, including cancer therapeutics. The present study evaluates the anticancer property of sericin from cocoons of <i>Antheraea proylei</i> J (SAP) against human lung cancer (A549) and cervical cancer (HeLa) cell lines. This is the first report of anti-cancer activity of the non-mulberry silkworm <i>A. proylei</i> J.</p><p><strong>Objective: </strong>Establish the antiproliferative potential of SAP. 2. Identify the molecular mechanism of cell death induced by SAP on two different cell lines.</p><p><strong>Aims: </strong>To investigate the anticancer activity of sericin preparation from cocoons of <i>A. proylei</i>.</p><p><strong>Methods: </strong>SAP was prepared from cocoons of <i>A. proylei</i> J. by the process of the degumming method. Cytotoxic activity was assessed by MTT assay, and genotoxicity was assessed by comet assay. Cleavage of caspase and PARP proteins and phosphorylation of MAPK pathway members were analysed by Western blotting. Cell cycle analysis was done by flow cytometer.</p><p><strong>Results: </strong>SAP causes cytotoxicity to A549 and HeLa cell lines with the IC₅₀ values 3.8 and 3.9 μg/μl respectively. SAP induces apoptosis in a dose-dependent manner through caspase-3 and p38, MAPK pathways in A549 and HeLa cells. Moreover, in A549 and HeLa cells, SAP induces cell cycle arrest at the S phase in a dose-dependent manner.</p><p><strong>Conclusion: </strong>The difference in the molecular mechanisms of apoptosis induced by SAP in A549 and HeLa cell lines may be due to the difference in the genotypes of the cancer cell lines. However, further investigation is warranted. The overall results of the present study envisage the possibility of using SAP as an anti-tumorigenic agent.</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":"9222866","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-proliferative, Morphological and Molecular Docking Studies of New Thiophene Derivatives and their Strategy in Ionic Liquids Immobilized Reactions.","authors":"Rafat M Mohareb, Sayeed Mukhtar, Humaira Parveen, Mahmoud A Abdelaziz, Ensaf S Alwan","doi":"10.2174/0118715206262307231122104748","DOIUrl":"10.2174/0118715206262307231122104748","url":null,"abstract":"<p><strong>Background: </strong>A number of research were conducted on the pyran and thiophene derivatives, which were attributed to have a wide range of biological activities, including anti-plasmodial, as well as acting as caspase, hepatitis C and cancer inhibitors.</p><p><strong>Objective: </strong>The multicomponent reactions of the 5-acetyl-2-amino-4-(phenylamino)-thiophene-3-carbonitrile produced biologically active target molecules like pyran and their fused derivatives. Comparison between regular catalytic multi-component reactions and solvent-free ionic liquids immobilized multicomponent was studied.</p><p><strong>Methods: </strong>The multicomponent reactions in this work were carried out not only under the reflux conditions using triethylamine as a catalyst but also in solvent-free ionic liquids immobilized magnetic nanoparticles (MNPs) catalysts.</p><p><strong>Results: </strong>Through this work, thirty-one new compounds were synthesized and characterized and were evaluated toward the six cancer cell lines, namely A549, HT-29, MKN-45, U87MG, and SMMC-7721 and H460. The most active compounds were further screened toward seventeen cancer cell lines classified according to the disease. In addition, the effect of compound 11e on the A549 cell line was selected to make further morphological changes in the cell line. The Molecular docking studies of 11e and 11f were carried and promising results were obtained.</p><p><strong>Conclusion: </strong>The synthesis of heterocyclic compounds derived from thiophene derivatives has been receiving significant attention. After a detailed optimizing study, it has been found that the solvent-free ionic liquids immobilized multi-component syntheses afforded a high yield of compounds, opening a greener procedure for this synthetically relevant transformation. Many of the synthesized compounds can be considered anticancer agents, enhancing further studies.</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":"139696833","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":"Design and Synthesis of Aspirin-chalcone Mimic Conjugates as Potential Anticancer Agents.","authors":"Reham A Mohamed-Ezzat, Aladdin M Srour","doi":"10.2174/0118715206280025231213065519","DOIUrl":"10.2174/0118715206280025231213065519","url":null,"abstract":"<p><strong>Background: </strong>Extensive research has been conducted on aspirin, a widely recognized NSAID medication, regarding its potential as an anticancer agent. Studies have revealed its ability to trigger cell death in different types of cancer cells.</p><p><strong>Methods: </strong>A set of aspirin-chalcone mimic conjugates 5a-k and 6a-d utilizing the freshly prepared acid chloride of aspirin moiety has been designed and synthesized. To evaluate the newly developed compounds, the NCI 60- cell line panel was employed to assess their anti-proliferative properties. Subsequently, cell cycle analysis was conducted along with an examination of the compounds' impact on the levels of p53, Bax, Bcl-2, active caspase- 3, and their inhibition mechanism of tubulin polymerization.</p><p><strong>Results: </strong>Derivative 6c displayed the best anticancer activity among the tested series while 6d was the best against breast cancer MDA-MB-468, therefore both of them were selected for the 5-dose stage, however, targeting MDA-MB-468, PI-flow cytometry of compound 6d proved the triggered cell growth arrest at the G1/S phase avoiding the mitotic cycle in MDA-MB-468 cells. Similarly, the upregulation of oncogenic parameters such as caspase-3, p53, and Bax/Bcl-2, along with the inhibition of PARP-1 enzyme level, was observed with compound 6d. This compound also exhibited a significant ability to induce apoptosis and disrupt the intracellular microtubule network through a promising activity as a tubulin polymerization inhibitor with IC₅₀ = 1.065 ± 0.024 ng/ml. Furthermore, to examine the manner in which compound 6d binds to the active pocket of the tubulin polymerization enzyme, a molecular docking study was conducted.</p><p><strong>Conclusion: </strong>The study indicated that compound 6d could be a powerful microtubule-destabilizing agent. Therefore, further research on 6d could be worthwhile.</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":"139416154","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}