Drug Research最新文献

{"title":"A Novel Ruthenium(II) Complex and its Synergistic Anti-Leukemia Activity with GidA Protein via Dual-Pathway Apoptosis.","authors":"Antony K T Infanta S, Thandeeswaran Murugesan, Anand Raj Dhanapal, Palaniswamy Muthuswamy, Angayarkanni Jayaraman","doi":"10.1055/a-2905-1945","DOIUrl":"https://doi.org/10.1055/a-2905-1945","url":null,"abstract":"<p><strong>Abstract: </strong>This study demonstrates the effective anticancer activity of a semi-synthetic complex integrating the GidA protein and the ruthenium(II) complex against K562 human leukemia cells. Monotherapy evaluation revealed exceptional cytotoxicity, with half-maximal inhibitory concentration values of 0.058 μg/mL for GidA (a novel topoisomerase II inhibitor) and 14.1 μg/mL for Ru(II). Subsequently, isobologram analysis of six combination ratios identified profound synergy in formulations with elevated Ru(II) concentrations (combinations 4 and 5; sum of the fractional inhibitory concentration=0.17-0.86). All these synergistic complexes induced up to 73.91% apoptosis, exceeding single-agent efficacy (<i>p</i><0.01), while minimizing necrosis (<20%). Besides, mechanistic studies revealed dual pathways: Ru(II) triggered reactive oxygen species-dependent apoptosis (2.8-fold reactive oxygen species surge at 30 min; <i>p</i><0.01), while GidA operated via reactive oxygen species-independent mechanisms. This semi-synthetic complex may involve Ru(II), potentially mediated by transferrin receptor overexpression for targeted uptake. Also, combination 5 (4×Ru(II):1×GidA) emerged as the lead candidate, reducing effective doses and potentially mitigating resistance. Overall, these findings establish GidA-Ru(II) complexes as first-in-class dual-mechanism agents with high translational potential for refractory leukemia, offering a strategic solution to chemotherapy limitations through rational synergy.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Method for the Determination of Alpelisib, a Novel Phosphatidylinositol 3-Kinase Inhibitor, and Its Application to a Pharmacokinetic Study in Mice.","authors":"Abhishek Dixit, Arunava Das","doi":"10.1055/a-2901-3150","DOIUrl":"https://doi.org/10.1055/a-2901-3150","url":null,"abstract":"<p><strong>Abstract: </strong>Alpelisib (BY719) is a phosphoinositide-3-kinase inhibitor that specifically targets phosphoinositide-3-kinase-alpha. This enzyme is part of the phosphoinositide-3-kinase/α-serine/threonine-protein kinase/mammalian target of rapamycin signaling pathway, which promotes cell growth and survival. Mutations in the phosphoinositide-3-kinase gene cause the phosphoinositide-3-kinase signaling pathway to become overactive, leading to uncontrolled cell growth and survival, which contributes to tumor development. By inhibiting phosphoinositide-3-kinase-alpha, alpelisib can slow tumor growth and kill cancer cells. The goal of this study was to develop and validate a new, sensitive, specific, and rapid liquid chromatography-tandem mass spectrometry method for measuring alpelisib in dried blood spots from both mice and humans. Filgotinib served as the internal standard, and all procedures adhered to regulatory standards. Alpelisib and the internal standard were measured using a Sciex triple quadrupole mass spectrometer in multiple reaction monitoring mode with positive-ion detection. The focus was on the parent-daughter mass-to-charge transitions of <i>m/z</i> 442.0→327.9 for alpelisib and <i>m/z</i> 426.2→291.2 for the internal standard. The linear range for alpelisib was 0.331-1026 ng/mL (<i>r</i>>0.990). This method successfully characterized the in vitro metabolic profiles and in vivo pharmacokinetics of alpelisib in mice. A strong correlation was found between dried blood spots and plasma concentrations, suggesting that dried blood spots can serve as an alternative to plasma for pharmacokinetic analysis.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protocatechuic Acid Ethyl Ester Protects Against Doxorubicin-induced Cardiotoxicity in Rats.","authors":"Leila Safaeian, Maryam Farsiabi, Zahra Haghighatian, Mansooreh Asghari-Varzaneh","doi":"10.1055/a-2829-7178","DOIUrl":"10.1055/a-2829-7178","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin, an anti-neoplastic agent, is linked with a risk of cardiotoxicity following acute or cumulative doses. Protocatechuic acid ethyl ester, as a natural phenolic acid derivative, inhibits a prolyl hydroxylase enzyme with iron-chelating and antioxidative properties. This study evaluated the effects of protocatechuic acid ethyl ester on cardiotoxicity induced by doxorubicin in an animal model.</p><p><strong>Methods: </strong>Male Wistar rats were pretreated orally with 50, 75, and 150 mg/kg of protocatechuic acid ethyl ester for 14 days. Cardiotoxicity was induced by the acute injection of doxorubicin (20 mg/kg) on the 10^th day. Recording of the electrocardiogram, assessment of serum parameters of aspartate aminotransferase, lactate dehydrogenase, creatine phosphokinase-MB, malondialdehyde and total antioxidant capacity as ferric reducing antioxidant power, and histopathological inspection of heart tissues were performed.</p><p><strong>Results: </strong>Protocatechuic acid ethyl ester at all doses prevented the increase in heart rate and the decrease in the R-R interval induced by doxorubicin. Higher doses of protocatechuic acid ethyl ester (75 and 150 mg/kg) were able to improve most of the serum and tissue parameters of cardiac injury. Protocatechuic acid ethyl ester at a dose of 150 mg/kg significantly reduced lactate dehydrogenase (<i>p</i><0.01), aspartate aminotransferase, creatine phosphokinase-MB, and heart weight (<i>p</i><0.001) and improved histopathological changes. It markedly reversed oxidative insult through decreasing malondialdehyde (<i>p</i><0.01) and increasing ferric reducing antioxidant power (<i>p</i><0.05).</p><p><strong>Conclusions: </strong>Findings of this study indicated that protocatechuic acid ethyl ester has noteworthy potential to mitigate the cardiotoxicity associated with doxorubicin, possibly through alleviating oxidative stress.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"131-138"},"PeriodicalIF":2.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linezolid-Induced Serotonin Release from QGP-1 Cells.","authors":"Takezo Tsutsumi, Hitoshi Kashiwagi, Shungo Imai, Yuki Sato, Shunsuke Nashimoto, Mitsuru Sugawara, Yoh Takekuma","doi":"10.1055/a-2815-4097","DOIUrl":"10.1055/a-2815-4097","url":null,"abstract":"<p><strong>Background: </strong>Nausea and vomiting are commonly reported side effects of long-term linezolid therapy, which is indispensable for tuberculosis and osteoarticular infections. Since the mechanism underlying the development of nausea and vomiting during linezolid treatment is unknown, this study aimed to explore the mechanisms by focusing on the monoamine oxidase-inhibiting effect of linezolid.</p><p><strong>Methods: </strong>In vitro serotonin release assays were performed using QGP-1 cells as a surrogate for enterochromaffin cells exposed to linezolid, the monoamine oxidase inhibitor clorgyline, and the known emetogenic agent cisplatin. Serotonin concentrations in the solutions were measured using an enzyme-linked immunosorbent assay. Clorgyline and cisplatin were administered simultaneously with linezolid to elucidate the serotonin release mechanism and confirm the synergistic effects. The intracellular Ca²⁺assays using Fura‑2 were also performed to assess whether serotonin release is mediated by Ca²⁺‑dependent exocytosis.</p><p><strong>Results: </strong>Linezolid exposure significantly increased serotonin release from QGP-1 cells in concentration- and time-dependent manners. Serotonin release also increased in the clorgyline exposure group, and the release of serotonin in the linezolid/clorgyline co-exposure group was higher than that in the single-exposure groups. In contrast, no significant serotonin release or synergistic effects were observed in the cisplatin/linezolid-exposed groups. The Ca²⁺assays demonstrated that linezolid exposure did not change intracellular Ca²⁺levels.</p><p><strong>Conclusions: </strong>Serotonin release was observed when QGP-1 cells were exposed to linezolid, an effect similar to that observed with the potent monoamine oxidase A inhibitor clorgyline. Furthermore, the Ca²⁺assays indicated that linezolid‑induced serotonin release occurs independently of Ca²⁺‑dependent exocytosis.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"125-130"},"PeriodicalIF":2.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Counteractive Effects of Diarylpropionitrile on Testosterone-Induced Benign Prostatic Hyperplasia in Rats via Targeting Key Androgenic, Angiogenic, Proliferative, and Inflammatory Mechanisms.","authors":"Ahmed Khalafa Ali, Ahmed Rahmah Abu-Raghif, Hayder Ridha-Salman","doi":"10.1055/a-2801-8227","DOIUrl":"10.1055/a-2801-8227","url":null,"abstract":"<p><strong>Background: </strong>Benign prostatic hyperplasia is a common public health problem in aging men across the globe. Diarylpropionitrile, a selective estrogen receptor-beta agonist, favorably regulates cell proliferation and inflammation, two major hallmarks of benign prostatic hyperplasia pathology.</p><p><strong>Objective: </strong>This study aimed to explore the mitigative impact of diarylpropionitrile on testosterone-induced benign prostatic hyperplasia in rats.</p><p><strong>Methods: </strong>Forty male rats were randomly divided into four groups (<i>n</i>=10): a normal control group, a benign prostatic hyperplasia group, a finasteride-treated group, and a diarylpropionitrile-treated group. After 4 weeks of treatment, macroscopic and microscopic features of prostatic hyperplasia and androgenic, proliferative, angiogenic, apoptotic, and inflammatory biomarkers were assessed.</p><p><strong>Results: </strong>Testosterone administration significantly increased prostate weight, prostatic index, and hyperplasia scores. Both diarylpropionitrile and finasteride effectively ameliorated the benign prostatic hyperplasia lesions by reversing these changes. Both treatments significantly lowered elevated prostatic dihydrotestosterone, 5-αR2, β-catenin, and proliferating cell nuclear antigen levels, demonstrating a strong anti-proliferative effect. They also attenuated the increased pro-inflammatory cytokines interleukin-6, interleukin-27, and prostaglandin E2 and growth factors transforming growth factor beta and vascular endothelial growth factor. Furthermore, both agents inhibited testosterone-induced estrogen receptor-beta upregulation, counteracted peroxisome proliferator-activated receptor gamma tissue protein, and boosted the expression of the anti-apoptotic marker B-cell lymphoma 2.</p><p><strong>Conclusions: </strong>Diarylpropionitrile alleviates testosterone-induced benign prostatic hyperplasia in rats by modulating key pathways associated with cellular proliferation and inflammation. Diarylpropionitrile, as an estrogen receptor-beta agonist, represents a promising alternative for the benign prostatic hyperplasia treatment through multi-targeted mechanisms.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"107-124"},"PeriodicalIF":2.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Sex and Fed State Differences on the Pharmacokinetics of Drugs in Humans.","authors":"Omaimah Najib, Naji Najib, Nasir Mohammed Idkaidek","doi":"10.1055/a-2867-0189","DOIUrl":"10.1055/a-2867-0189","url":null,"abstract":"<p><strong>Background: </strong>Sex and fed state are critical factors influencing drug pharmacokinetics, potentially affecting efficacy and safety. This study evaluates the impact of sex and food intake on key pharmacokinetics parameters-maximum plasma concentration, time to maximum plasma concentration, area under the curve to last time point, area under the curve extrapolated to infinity, and elimination half-life-for amlodipine, dapagliflozin, empagliflozin, rivaroxaban, deferiprone, deflazacort, and siponimod.</p><p><strong>Methods: </strong>Pooled data from clinical studies were analyzed. Geometric mean values and coefficients of variation were calculated for men and women. Statistical comparisons were performed using appropriate tests to derive <i>p</i>-values for sex (men vs women) and fed state (fasting vs fed) differences.</p><p><strong>Results: </strong>Significant sex-based differences were observed. Women exhibited significantly higher systemic exposure (the maximum plasma concentration and area under the curve) for amlodipine, dapagliflozin, empagliflozin, rivaroxaban (in the fed state and overall), deferiprone (overall and fed), and siponimod (overall and fasting). The time to the maximum plasma concentration was significantly faster for deflazacort in women. Fed state comparisons showed that food significantly increased the time to the maximum plasma concentration for deferiprone in both sexes and rivaroxaban in women, while decreasing the maximum plasma concentration for rivaroxaban in both sexes.</p><p><strong>Conclusions: </strong>Sex and fed state significantly influence the pharmacokinetics of several drugs. These findings underscore the necessity of considering these factors in clinical dosing regimens and drug development to optimize therapeutic outcomes.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"139-144"},"PeriodicalIF":2.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ellagic Acid Attenuates Doxorubicin-induced Cardiomyocyte Ferroptosis Via Nuclear Factor Erythroid 2-Related Factor 2 Signaling.","authors":"Rong Li, Zhong Cheng, Wei Li","doi":"10.1055/a-2873-4789","DOIUrl":"10.1055/a-2873-4789","url":null,"abstract":"<p><strong>Abstract: </strong>Doxorubicin, a widely used chemotherapeutic agent, is clinically limited by its dose-dependent cardiotoxicity, in which cardiomyocyte ferroptosis has recently been identified as a critical pathogenic mechanism. Consequently, targeting myocardial ferroptosis has emerged as a promising strategy to reduce doxorubicin-induced cardiac injury. Ellagic acid, a naturally occurring polyphenolic compound, possesses potent antioxidant and anti-inflammatory properties that contribute to its cytoprotective effects. This study aimed to investigate the protective role of ellagic acid against doxorubicin-induced cardiomyocyte ferroptosis and elucidate its underlying mechanisms. Using H9C2 cells and human-induced pluripotent stem cell-derived cardiomyocytes, we established in vitro models of doxorubicin-induced cardiac ferroptosis. Ellagic acid treatment markedly upregulated the expression of anti-ferroptosis proteins, reduced reactive oxygen species accumulation, and alleviated lipid peroxidation, thereby suppressing doxorubicin-triggered ferroptosis. Moreover, the anti-ferroptosis effects of ellagic acid were validated in vivo. Mechanistically, these cardioprotective actions were mediated through the activation of the nuclear factor erythroid 2-related factor 2 signaling pathway. In conclusion, our findings identify ellagic acid as a novel nuclear factor erythroid 2-related factor 2 activator that protects against doxorubicin-induced cardiotoxicity by inhibiting ferroptosis in cardiomyocytes.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"145-158"},"PeriodicalIF":2.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Effects of Curcumin and Temozolomide in Overcoming Glioblastoma Drug Resistance through Regulation of O6-Methylguanine-DNA Methyltransferase, Mismatch Repair, and Poly(Adenosine Diphosphate Ribose) Polymerase 1.","authors":"Masoud Sohrabi, Amir Valizadeh, Mehran Molavand, Bahman Yousefi, Mohammad Shimia","doi":"10.1055/a-2800-2050","DOIUrl":"10.1055/a-2800-2050","url":null,"abstract":"<p><strong>Background and objective: </strong>Glioblastoma is one of the most frequently seen cancer types in the central nervous system, which is associated with drug resistance and high mortality rates. Curcumin demonstrates significant anticancer potential by inhibiting crucial processes, such as cell proliferation and metastasis, positioning it as a candidate for targeted treatment strategies. In this study, the potential of curcumin to overcome temozolomide resistance in U87 glioblastoma cells was examined, with a focus on elucidating the underlying molecular pathways.</p><p><strong>Methods: </strong>U87 and U87/TMZ cells were treated with different concentrations of curcumin, temozolomide, and their combination for 24 and 48 hours, and the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to assess viability. The expression of key genes and proteins of the Bax, Bcl-2, caspase-3, O6-methylguanine-DNA methyltransferase, and DNA repair genes, including <i>MSH2</i>, <i>MSH6</i>, and <i>PARP1</i>, was evaluated by quantitative real-time polymerase chain reaction and western blot. Also, the activity of caspase-3/7 enzymes and the level of apoptosis were measured by fluorometric methods and enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>Curcumin significantly decreased temozolomide-resistant U87 cell viability in combination with temozolomide in a dose-dependent manner. The expression of O6-methylguanine-DNA methyltransferase, <i>MSH2</i>, <i>MSH6</i>, and <i>PARP1</i> genes and proteins was decreased. Also, the increase in Bax expression and caspase activity indicated a strong induction of apoptosis by curcumin in resistant cells.</p><p><strong>Conclusions: </strong>Curcumin mitigates temozolomide resistance in glioblastoma by modulating the O6-methylguanine-DNA methyltransferase/MSH2/MSH6 axis and enhancing apoptosis. This natural compound holds promise as a potential agent for the development of targeted glioblastoma therapies.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Janus Kinase Inhibitors for Vitiligo Treatment.","authors":"Wanlin Wang, Yue Liao, Ruizhi Zhang, Jijun Huang, Jiamin Liu, Xiaokang Shan, Xiaojing Gao, Jin Bu, Yaping Tang, Erxia Shen","doi":"10.1055/a-2784-6722","DOIUrl":"10.1055/a-2784-6722","url":null,"abstract":"<p><p>Vitiligo is a cutaneous autoimmune disease characterized by the destruction of epidermal melanocytes leading to white patches with a global prevalence of about 0.5-2%, and patients' quality of life are greatly affected by the change in appearance and social discrimination caused by the disease. Most of the key cytokines in the pathogenesis of vitiligo act through the Janus kinase/signal transducer and activator of transcription signaling pathway, which is an effective therapeutic target. The first generation Janus kinase inhibitors, i.e., tofacitinib and ruxolitinib, inhibit a variety of Janus kinases, whereas the new generation Janus kinase inhibitors, such as ritlecitinib and upadacitinib, exhibit inhibitory effects only on specific Janus kinases; they are therefore selective as well as safer and more effective. In this review, we aim to provide an up-to-date view of vitiligo pathogenesis at the cellular, molecular, and genetic levels and further to elucidate the relationship between Janus kinase/signal transducer and activator of transcription signaling pathway components and vitiligo. Finally, we summarize currently market-approved and preclinical Janus kinase inhibitors, highlighting the latest advances in their clinical applications.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"57-64"},"PeriodicalIF":2.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intramolecular Interactions of Twenty-Eight Amide Derivatives with the C-ALB Kinase using a Theoretical Model as a Therapeutic Alternative to Treat Cancer.","authors":"Marcela Rosas-Nexticapa, Magdalena Alvarez-Ramirez, Maria Virginia Mateu-Armad, Enrique Bonilla Zavaleta","doi":"10.1055/a-2793-9663","DOIUrl":"10.1055/a-2793-9663","url":null,"abstract":"<p><p>Several studies have shown that some drugs can slow the growth of cancer cells by inhibiting the c-Abl kinase. However, some of these drugs can cause side effects such as gynecomastia, pulmonary toxicity, and lentiginosis, among others. In the search for a therapeutic alternative, some amide derivatives have been developed to treat cancer. However, their interaction with the c-Abl kinase is not clear.The aim of this study was to evaluate the interaction of 28 amide derivatives with the c-Abl kinase as a therapeutic alternative to treat cancer cells.The theoretical interaction of amide derivatives with the c-Abl kinase was carried out using the 1iep protein as a theoretical model. Besides, bosutinib, dasatinib, imatinib, nilotinib, and radotinib were used as controls in the DockingServer program.The results displayed different types of aminoacid residues involved in the interaction of amide derivatives with the 1iep protein surface compared to the controls. In addition, the inhibition constant (Ki) was lower for compounds 15, 16, and 18 compared to radotinib. Finally, the Ki for amide derivatives 1, 19, and 21 were lower compared with bosutinib, dasatinib, imatinib, and nilotinib.Theoretical data indicate that amide derivatives such as 1, 15, 16, 18, 19, and 21 might have a higher affinity for the 1iep protein surface. This phenomenon could be translated as c-Abl kinase inhibition, resulting in a decrease in cancer cell growth.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"91-98"},"PeriodicalIF":2.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}