Anti-cancer agents in medicinal chemistry最新文献

{"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}

{"title":"In vivo, In vitro, and In silico Studies of Umbelliferone and Irinotecan on MDA-MB-231 Breast Cancer Cell Line and Drosophila melanogaster Larvae.","authors":"Erkut Tamtürk, Serap Yalcin, Fahriye Ercan, Aydın Tunçbilek","doi":"10.2174/0118715206340868241018075528","DOIUrl":"https://doi.org/10.2174/0118715206340868241018075528","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;Deaths from cancer are still very common all over the world and continue to be the focus of scientific research. Chemotherapy is one of the primary treatments used to prevent deaths from cancer. Side effects of chemotherapeutic drugs and resistance of cells to drugs are essential problems that limit the treatment process. Drug combination therapy is regarded as a significant application that inhibits the growth of tumors and is anticipated to provide a solution for the issues encountered. The combination therapy aims at a synergistic effect that will limit drug resistance and cytotoxic effects with appropriate drug combinations. In this context, we aim to investigate the in vitro, in vivo, and in silico effects of single and combined doses of umbelliferone and irinotecan, known for their anticarcinogenic and curative effects, on MDA-MB-231 breast cancer cell lines and the model organism Drosophila melanogaster.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Irinotecan is currently used as an anticarcinogenic drug. Anticarcinogenic effects of umbelliferone have also been detected. The in vivo, in vitro, and in silico impacts of single and combined doses use of these two agents are not yet available in the literature.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to determine the anticarcinogenic effects of single and combined use of umbelliferone and irinotecan at the molecular level. It also attempts to determine the binding energies of chemicals to cancerrelated proteins through docking and molecular dynamic studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;The cytotoxic effects of individual and combinational doses of umbelliferone and irinotecan on the MDAMB- 231 cell line and D. melanogaster were calculated by XTT and probit analyses. IC50 values for the cancer cells, LC50, and LC99 values for D. melanogaster were found. Gene expression analysis was performed to determine the effects of chemical agents on miR-7, miR-11, and miR-14, and their expression levels were found. The sequences of miRNAs not found in the literature were determined, and their molecular imaging was performed. In addition, the binding energies of irinotecan and umbelliferone to Bcl-2, Bad, and Akt1 proteins, which are known to have apoptotic effects, were found by the molecular docking method. Molecular dynamics studies of Bad proteins and chemicals were also performed. The drug potential of chemicals was determined by ADME/T analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;The cytotoxic effect on cells was calculated, and the IC50 value of umbelliferone was calculated as 158 μM, the IC50 value of irinotecan was calculated as 48,3 μM and the IC50 value was calculated as 20 μM. In the probit analysis performed to calculate the cytotoxic effects of drugs on D. melanogaster, the LC50 value of umbelliferone was 2,5 μM, and the LC99 value was 13,4 μM. The LC50 value of irinotecan was found to be 0,1 μM, and the LC99 value was 0,28 μM. It was concluded that single and combined ","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":"142543223","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":"PEGylated Titanium Dioxide Nanoparticle-bound Doxorubicin and Paclitaxel Drugs Affect Prostate Cancer Cells and Alter the Expression of DUSP Family Genes.","authors":"Zuhal Tunçbilek, Neşe Keklikçioğlu Çakmak, Ayça Taş, Durmuş Ayan, Yavuz Siliğ","doi":"10.2174/0118715206330115241015092548","DOIUrl":"https://doi.org/10.2174/0118715206330115241015092548","url":null,"abstract":"<p><strong>Background: </strong>PC is among the cancer types with high incidence and mortality. New and effective strategies are being sought for the treatment of deadly cancers, such as PC. In this context, the use of nanocarrier systems containing titanium dioxide can improve treatment outcomes and increase the effectiveness of anticancer drugs.</p><p><strong>Objective: </strong>This study aimed to evaluate the cytotoxic activity of doxorubicin (DOX) and paclitaxel (PTX) drugs on the prostate cancer (PC) cell line by attaching them to pegylated titanium dioxide nanoparticles and to examine their effect on the expression levels of dual-specificity phosphatase (DUSP) genes.</p><p><strong>Methods: </strong>Free DOX and PTX drugs, DOX and PTX compounds bound to the pegylated titanium dioxide system were applied to DU-145 cells, a PC cell line, under in vitro conditions, and MTT analysis was performed. Additionally, the IC50 values of these compounds were analyzed. In addition, the expression levels of DUSP1, DUSP2, DUSP4, DUSP6, and DUSP10 genes were measured using RT-PCR. Additionally, bioinformatics and molecular docking analyses were performed on DUSP proteins.</p><p><strong>Results: </strong>The cytotoxic activity of PTX compound bound to PEGylated TiO2 was found to be higher than that of DOX compound bound to PEGylated TiO2. Additionally, when the expression levels were compared to the control group, the expression levels of DUSPs were found to be lower in the drugs of the drug carrier systems.</p><p><strong>Conclusion: </strong>Accordingly, it was predicted that the pegylated titanium dioxide nano-based carrier could be effective in PC.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543225","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":"Current Insights into Therapeutic Potential of Terpenoids as Anticancer Agents.","authors":"Biswa Mohan Sahoo, Bimal Krishna Banik, Shikha Sharma, Bhupendra Singh","doi":"10.2174/0118715206342920241008062115","DOIUrl":"https://doi.org/10.2174/0118715206342920241008062115","url":null,"abstract":"<p><strong>Background: </strong>Cancer is regarded as one of the main causes of death globally. Future predictions indicate that the death rate from cancer will keep rising, which may reach 11.4 million in 2030. Carcinogenesis refers to the phenomenon of transforming a normal cell into a cancer cell. Cancer is characterized by unregulated and uncontrolled cell division due to alterations at the molecular and genetic levels. Gene mutations can speed up the rate of cell division, which leads to cancer. Metastasis entails the dissemination of cancer cells from the primary site to distant regions of the body via the circulatory or lymphatic systems.</p><p><strong>Objective: </strong>This review is mainly focusing on the anticancer properties of terpenoids. In the case of human beings, several types of cancers can be treated clinically based on the form and phase of the cancer. So, there are different types of treatment regimens available for the management of cancer, such as immunotherapy, hormonal therapy, radiation therapy, and chemotherapy.</p><p><strong>Methods: </strong>Several problems are associated with cancer therapy, including chemoresistance, severe toxicity, relapse, and metastasis. To minimize these complications, natural products like terpenoids seem to be beneficial for the effective management of cancer.</p><p><strong>Results: </strong>Experimental results revealed that the anticancer potential of terpenoids is due to activation of apoptosis and stimulation of cell cycle arrest. Some of the terpenoids exhibit anticancer effects by inhibiting angiogenesis and metastasis via the regulation of several signaling pathways intracellularly. Certain terpenoids have been shown to work in concert with anticancer medications (doxorubicin, cisplatin, paclitaxel, and 5-fluorouracil) to provide synergistic effects. These terpenoids have also been shown to be effective against cancer cells that are resistant to several drug therapies.</p><p><strong>Conclusion: </strong>The current study will focus on signaling pathways and mode of action of several types of terpenoids as anticancer agents. Further, it will provide insights into the ongoing clinical trials and prospective pathways for the advancement of terpenoids as possible anti-cancer agents.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493101","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 Mesoionic 1,3,4-thiadiazolium Derivative, MI-D, is a Potential Drug for Treating Glioblastoma by Impairing Mitochondrial Functions Linked to Energy Provision in Glioma Cells.","authors":"Marília Locatelli Corrêa-Ferreira, Amanda do Rocio Andrade Pires, Juan Vitor Miranda, Eduardo de Freitas Montin, Igor Resendes Barbosa, Aurea Echevarria Aznar Neves Lima, Maria Eliane Merlin Rocha, Glaucia Regina Martinez, Sílvia Maria Suter Correia Cadena","doi":"10.2174/0118715206329159241010052746","DOIUrl":"https://doi.org/10.2174/0118715206329159241010052746","url":null,"abstract":"<p><strong>Background: </strong>Mesoionic compound MI-D possesses important biological activities, such as antiinflammatory and antitumoral against melanoma and hepatocarcinoma. Glioblastoma is the most aggressive and common central nervous system tumor in adults. Currently, chemotherapies are not entirely effective, and the survival of patients diagnosed with glioblastoma is extremely short.</p><p><strong>Objective: </strong>In this study, we aimed to evaluate the cytotoxicity of MI-D in noninvasive A172 glioblastoma cells and establish which changes in functions linked to energy provision are associated with this effect.</p><p><strong>Methods: </strong>Cells A172 were cultured under glycolysis and phosphorylation oxidative conditions and evaluated: viability by the MTT method, oxygen consumption by high-resolution respirometry, levels of pyruvate, lactate, citrate, and ATP, and glutaminase and citrate synthase activities by spectrophotometric methods.</p><p><strong>Results: </strong>Under glycolysis-dependent conditions, MI-D caused significant cytotoxic effects with impaired cell respiration, reducing the maximal capacity of the electron transport chain. However, A172 cells were more susceptible to MI-D effects under oxidative phosphorylation-dependent conditions. At the IC25, inhibition of basal and maximal respiration of A172 cells was observed, without stimulation of the glycolytic pathway or Krebs cycle, along with inhibition of the activity of glutaminase enzyme, resulting in a 30% ATP deficit. Additionally, independent of metabolic conditions, MI-D treatment induced cell death in A172 cells by apoptosis machinery/ processes.</p><p><strong>Conclusion: </strong>The impairment of mitochondrial respiration by MI-D under the condition sustained by oxidative phosphorylation may enhance the cytotoxic effect on A172 glioma cells, although the mechanism of cell death relies on apoptosis.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493102","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":"Doramectin Induces Apoptosis in B16 Melanoma Cells.","authors":"Megan S Crotts, Jena C Jacobs, Robert W Baer, James L Cox","doi":"10.2174/0118715206325844240909144543","DOIUrl":"https://doi.org/10.2174/0118715206325844240909144543","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Metastatic melanoma resists current pharmacological regimens that act through apoptosis. This indicates that therapies acting via non-apoptotic cell-death pathways could be pursued. Doramectin has shown promising results in another cancer of neural crest origin, neuroblastoma, through the inhibition of growth via autophagy. Our research hypothesis is that doramectin induces autophagy in B16F10 melanoma cells.</p><p><strong>Methods: </strong>Cells were treated with doramectin (15 uM) or a combination of both doramectin and a cell-death inhibitor, compared to untreated control cells (media), and then analyzed with MTT analysis. Likewise, MDC analysis was completed to detect autophagy involvement with doramectin treatment. Flow cytometry and TUNEL Assay were conducted to observe cell death-related effects.</p><p><strong>Results: </strong>MTT analysis of doramectin-treated cells displayed a decrease in cell growth compared to control. Apoptotic morphology was prominent in melanoma cells treated with doramectin. Increased autophagy was not detected by fluorometric microscopic analysis. Flow cytometry analysis of doramectin-treated cells showed apoptosis as a major mode of cell death with some necrosis.</p><p><strong>Conclusion: </strong>Doramectin induces a novel cell-death mechanism in melanoma compared to other forms of cancer and should be studied as an effective anti-cancer agent for melanoma treatment.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456331","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}