European Journal of Medicinal Chemistry Reports最新文献

{"title":"MolAnchor method for explaining compound predictions based on substructures","authors":"Alec Lamens ,&nbsp;Jürgen Bajorath","doi":"10.1016/j.ejmcr.2024.100230","DOIUrl":"10.1016/j.ejmcr.2024.100230","url":null,"abstract":"<div><div>In medicinal chemistry, the impact of machine learning remains limited if predictions are not understood, which often precludes experimental follow-up. Therefore, chemically intuitive approaches that aid in model understanding and interpretation at the molecular level of detail are sought after. While feature attribution methods quantifying feature importance for model decisions are widely used in many areas, they must typically be combined with visualization techniques, if possible, to render the results accessible from a chemical viewpoint. On the other hand, there are approaches such as counterfactuals that yield closely related chemical structures with different prediction outcomes, providing direct access to structural features that critically influence model decisions. Herein, we introduce another approach designed to rationalize chemical predictions based on molecular structure. Therefore, we adapt principles underlying the anchor concept from explainable artificial intelligence (XAI) and alter them for molecular machine learning. The resulting method, termed MolAnchor, systematically identifies substructures in test compounds that determine property predictions, thus ensuring chemical interpretability. The MolAnchor methodology is made freely available to the medicinal chemistry community as a part of our study.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100230"},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovering bioactive phytoconstituents from Citrullus lanatus for antimicrobial and antioxidants therapeutic applications","authors":"Lakshmana Nakkalagadda Venkataravana,&nbsp;Jagadesh Uppin,&nbsp;Nikhitha Chinna Ramanjineyulu,&nbsp;Poojitha Gowribidanur Krishna,&nbsp;Jayaram Lakshmaiah Narayana","doi":"10.1016/j.ejmcr.2024.100229","DOIUrl":"10.1016/j.ejmcr.2024.100229","url":null,"abstract":"<div><div>In recent decades, significant interest in natural bioactive compounds has led many researchers to study plants as primary natural sources of bioactive compounds, mainly when considering a few biological properties, including antioxidant, antimicrobial, and anti-inflammatory activities, and as nutritional supplements with health benefits. We designed this study to explore the phytochemicals profiling of <em>Citrallus lanatus</em> and evaluate their <em>in vitro</em> bioactive properties<em>.</em> The methanol extraction of the watermelon's stem, rind, and leaf parts through Soxhlet extraction was analyzed using Gas Chromatography-Mass Spectrometry. The GC-MS profiling of <em>Citrullus lanatus</em> examines the presence of numerous bioactive phytoconstituents with potential biological activities such as antioxidant, anti-inflammatory, antimicrobial, anticancer, and other properties. We have evidenced that the stem, rind, and leaf extracts with significant antioxidant and antimicrobial activities against clinically relevant pathogens like <em>Salmonella typhi</em>, <em>Pseudomonas aeruginosa</em>, <em>Bacillus subtilis</em>, and <em>Staphylococcus aureus</em>. Overall, our study sheds light on exploring novel bioactive phytoconstituents from C<em>itrullus lanatus</em> and explore, harness these compounds' therapeutic potential for human health.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100229"},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination of heme oxygenase-1 inhibitors and temozolomide to improve the anticancer effect in glioblastoma","authors":"Sebastiano Intagliata ,&nbsp;Valeria Ciaffaglione ,&nbsp;Valeria Consoli ,&nbsp;Agata Grazia D'Amico ,&nbsp;Luca Vanella ,&nbsp;Valeria Pittalà ,&nbsp;Federica Sodano ,&nbsp;Marica Erminia Schiano ,&nbsp;Valeria Sorrenti ,&nbsp;Loredana Salerno","doi":"10.1016/j.ejmcr.2024.100227","DOIUrl":"10.1016/j.ejmcr.2024.100227","url":null,"abstract":"<div><div>Heme oxygenase-1 (HO-1) is involved in the oncogenesis of glioblastoma (GBM). In this work, we investigated for the first time how the co-administration (combo) of the HO-1 inhibitors <strong>SI1/09</strong> or <strong>LS6/42</strong> with temozolomide (<strong>TMZ</strong>) or temozolomide acid (<strong>TMZ Ac</strong>) may influence the proliferation of U87MG GBM cell lines. Moreover, two novel TMZ/HO-1 inhibitors codrugs <strong>LS8/21</strong> and <strong>LS8/24</strong> were synthesised, characterised and tested. Results indicate that the combos <strong>TMZ</strong> or <strong>TMZ Ac</strong> with <strong>LS6/42</strong>, as well as the corresponding <strong>LS8/24</strong>, are more efficacious in reducing U87MG cell proliferation with respect to reference drugs, allowing a possible reduction of the <strong>TMZ</strong> dosage and related side effects in clinical practice. The chemical and enzymatic stability of the most potent codrug <strong>LS8/24</strong> was evaluated. The observed high potency performed by both combos and <strong>LS8/24</strong> in cells suggests that HO-1 inhibition may give additional contribution to the antiproliferative effect of <strong>TMZ</strong>.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100227"},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological properties and in silico studies of thiazolopyrimidine derivatives active against visceral and cutaneous Leishmania spp. amastigote forms","authors":"Gulsah Bayraktar ,&nbsp;Pascal Marchand ,&nbsp;Euzébio Guimarães Barbosa ,&nbsp;Marilia Cecilia da Silva ,&nbsp;Karen Cacilda Weber ,&nbsp;Sandrine Cojean ,&nbsp;Merve Saylam ,&nbsp;Huseyin Istanbullu","doi":"10.1016/j.ejmcr.2024.100228","DOIUrl":"10.1016/j.ejmcr.2024.100228","url":null,"abstract":"<div><div>Visceral leishmaniasis, the most severe form of the disease, is caused by <em>L. donovani</em> and <em>L. infantum</em> parasites; cutaneous leishmaniasis is the most common endemic form of leishmaniasis and mainly caused by <em>L. tropica</em> and <em>L. major</em>. We have previously described a series of thiazolopyrimidine derivatives and reported their antipromastigote activities against various parasites. In this study, we also investigated their activities against <em>L. donovani</em> and <em>L. major</em> axenic amastigotes, intramacrophage amastigotes and cytotoxicity on macrophages to assess selectivity. As a result, five of the compounds tested showed no cytotoxicity on the macrophage cell line; their anti-amastigote activity was close to the positive control, miltefosine. These results confirm the antileishmanial activity of the thiazolopyrimidine scaffold and demonstrate that this may be a starting point for the generation of new lead compounds for treating visceral leishmaniasis and cutaneous leishmaniasis. To elucidate the mechanism of action, we also performed several ligand- and structure-based <em>in silico</em> studies.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100228"},"PeriodicalIF":0.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combinational delivery of berbamine and 5-fluorouracil in cerium oxide nanoparticles for colon cancer therapy: Insights from in vitro and in silico studies","authors":"Sneha Shriparna Satpathy ,&nbsp;Sweta Mishra ,&nbsp;Saswati Pattnaik,&nbsp;Chandana Mohanty","doi":"10.1016/j.ejmcr.2024.100224","DOIUrl":"10.1016/j.ejmcr.2024.100224","url":null,"abstract":"<div><div>Colon cancer is traditionally treated by an antimetabolite drug 5-fluorouracil (5FU) but has been linked to several drawbacks and systemic toxicity. To overcome drug associated toxicity, combination therapy is a promising strategy that synergistically enhances the therapeutic effects of co-delivered drugs while minimizing administration doses. Therefore, the current study aims to investigate the anti-colon cancer potency of 5FU co-delivered with a phytochemical i.e., berbamine (BERB) in a Cerium oxide nanoparticles (CONPs) delivery system. CONPs loaded 5FU (5FU-CONPs) and BERB (BERB-CONPs) were prepared and characterized using different analytical techniques. Successful entrapment of both drugs into CONPs formulations was detected under X-ray diffraction (XRD) observations. Drug-loaded CONPs in combination showed effective anti-oxidant activity by preventing reactive oxygen species (ROS) generations and had superior cytotoxic effects on HT-29 cell lines compared to treatment with native drugs singly or in combination. They also triggered apoptosis through p21, p53, Bax upregulation, and Bcl-2 downregulation, as confirmed by western blot studies. Additionally, <em>in silico</em> analysis was performed using molecular docking and molecular dynamics simulation (MDS) to validate the <em>in vitro</em> results. Results of the study suggest that 5FU and BERB CONPs in combination could be taken as a possible therapeutic approach for colon cancer treatment.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100224"},"PeriodicalIF":0.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer α-, γ-, and δ-carboline derivatives: structures, mechanisms of action, and SARs","authors":"Jingliang Cui,&nbsp;Wanru Gao,&nbsp;Ziwei Liu,&nbsp;Shuang Cao,&nbsp;Sihui Long","doi":"10.1016/j.ejmcr.2024.100221","DOIUrl":"10.1016/j.ejmcr.2024.100221","url":null,"abstract":"<div><div>Carboline consists of a pyridine ring fused with an indole skeleton, and it serves as a potential drug scaffold. Depending on the relative position of the pyridine N to the indole N, carbolines can be categorized into <em>α-, β-, γ-,</em> and <em>δ</em>-subfamilies. They have diverse pharmacological activities, such as anticancer, antimalaria, antibacterial, antifungal, anti-Alzheimer's disease, etc. Among them, <em>β</em>-carbolines are the most widely studied and are also well reviewed. Herein, we review the anticancer activity of <em>α-, γ-,</em> and <em>δ</em>-carboline natural products and their synthetic derivatives, as they provide new inroads for cancer therapy. Particularly, we highlight the new derivatives of <em>α-, γ-,</em> and <em>δ</em>-carboline with anticancer activity, and their anticancer mechanisms, as well as structure-activity relationship. Meanwhile, we propose strategies for the development of new <em>α-</em>, <em>γ-</em>, and <em>δ</em>-carboline derivatives for cancer therapy.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100221"},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review on progress of thiazole derivatives as potential anti-inflammatory agents","authors":"Kereyagalahally H. Narasimhamurthy ,&nbsp;Toreshettahally R. Swaroop ,&nbsp;Kanchugarakoppal S. Rangappa","doi":"10.1016/j.ejmcr.2024.100225","DOIUrl":"10.1016/j.ejmcr.2024.100225","url":null,"abstract":"<div><div>Inflammation is a body response against infection that activates other biological components that include various cytokines, chemokines and other biological compounds that trigger body response against pathological activities. The Arachidonic acid pathway is involved in the inflammation that is connected with lipoxygenase (LOX) and cyclooxygenase (COX) enzymes. The importance of the isoforms of LOX and COX in inflammation is well studied. At the cellular level, some of the thiazole derivatives showed potent anti-inflammatory activities especially to block LOX5 and COX2 in the inflammation. These factors include both acute and chronic inflammation in various tissues like the heart, kidney, pancreas, brain, intestine, lungs and other organs as well that lead to the damage of the organs or cells. Whether it's the infectious or non-infectious response it will further activate some of the downstream signaling pathways like lipoxygenase, cyclooxygenase, cytochrome 450, JAK-STAT, MAPK, JNK, TNF-α, Nfr2, and many more pathways that lead to activation of another chronic disease in the body. In this review, we will concentrate on thiazole molecules that serve as anti-inflammatory responses to both acute and chronic inflammation. Further, we discussed the evidence that correlates the possible connection with LOX and COX enzymes in the inflammatory pathways and their blocking ability especially through thiazole derivatives has been discussed in this present review. The current assessment is the best part of the present consequence of thiazole derivatives on anti-inflammatory studies, covering articles published from 1973 to 2023.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100225"},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of novel favipiravir derivatives with improved pharmacokinetic properties as anti-SFTSV agents","authors":"Xiaomeng He ,&nbsp;Fan Wu ,&nbsp;Wei Li ,&nbsp;Runze Zhang ,&nbsp;Ruiyang Sun ,&nbsp;Zhihong Hu ,&nbsp;Wu Zhong ,&nbsp;Manli Wang","doi":"10.1016/j.ejmcr.2024.100226","DOIUrl":"10.1016/j.ejmcr.2024.100226","url":null,"abstract":"<div><div>Favipiravir is a nucleobase analogue that exhibits antiviral activities against a variety of RNA viruses. Due to the lack of antivirals to combat SFTS, an emerging tickborne epidemic caused by a RNA virus belonging to the Phenuividae family within Bunyavirales, Favipiravir has been put brand new attention as optimal SFTS clinical candidate. We here disclose chemical synthesis of novel derivatives of Favipiravir. All derivatives showed favorable inhibitory effect on SFTSV replication <em>in vitro</em>. The 50 % effective concentration (EC₅₀) of the most active compound <strong>H3</strong> was 12.06 μM, better than that of Favipiravir (15.51 μM). Most importantly, compared with the clinical candidate Favipiravir, pharmacokinetic studies conducted on rats demonstrated enhanced pharmacokinetic properties for <strong>H2</strong> and <strong>H3</strong> including parameters of T_1/2, C_max and AUC. These combined attributes identified novel promising drug candidates for the treatment of SFTSV infection.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100226"},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Truncated NPY-based NPY(Y1)R-specific radiopeptides: Improved in vivo PET tumor imaging by application of peptidase inhibitors","authors":"Benedikt Judmann ,&nbsp;Nils F. Baier ,&nbsp;Henning Rudolf ,&nbsp;Güllü Davarci ,&nbsp;Björn Wängler ,&nbsp;Ralf Schirrmacher ,&nbsp;Gert Fricker ,&nbsp;Carmen Wängler","doi":"10.1016/j.ejmcr.2024.100223","DOIUrl":"10.1016/j.ejmcr.2024.100223","url":null,"abstract":"&lt;div&gt;&lt;div&gt;The neuropeptide Y receptor subtype 1 (NPY(Y&lt;sub&gt;1&lt;/sub&gt;)R) exhibits high expression rates on human breast cancer and is therefore an important target structure for the sensitive and specific visualization and characterization of the disease by Positron Emission Tomography (PET). However, imaging of this receptor type has been of limited success so far due to the low stability of peptide-based NPY-derived NPY(Y&lt;sub&gt;1&lt;/sub&gt;)R-specific radiotracer candidates due to &lt;em&gt;in vivo&lt;/em&gt; degradation. Given the challenges in stabilizing these agents, our study sought to explore whether the stability of NPY(Y&lt;sub&gt;1&lt;/sub&gt;)R-specific radiopeptides could be enhanced. We aimed to achieve this by either modifying the peptide structure with various molecular scaffolds or by applying peptidase inhibitors. This evaluation aimed to identify the optimal approach for achieving effective NPY(Y&lt;sub&gt;1&lt;/sub&gt;)R-specific imaging in the following. To validate our approach, we systematically investigated four new truncated &lt;sup&gt;68&lt;/sup&gt;Ga-labeled analogs of NPY and the reference compound [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-[Lys&lt;sup&gt;4&lt;/sup&gt;(N&lt;sub&gt;ε&lt;/sub&gt;-DOTA)]BVD15, bearing different molecular scaffolds such as a DOTA or NODA-GA chelator, a 4-APipAc linker, a Bip unit, and an &lt;em&gt;N&lt;/em&gt;-terminal Lys(lauryl) group. The four new radiotracers as well as the reference compound were obtained in high chemical and radiochemical yields with molar activities of 33–39 GBq/μmol. The radiopeptides exhibited varying log&lt;sub&gt;&lt;em&gt;D&lt;/em&gt;7.4&lt;/sub&gt; values, ranging from −3.37 ± 0.09 to +0.35 ± 0.11, and showed different levels of stability in human serum and liver microsomes, depending on their molecular structure. Subsequently, the influence of the peptidase inhibitors actinonin, phosphoramidon, captopril and E−64 on the &lt;em&gt;in vitro&lt;/em&gt; stability of the radiotracers was investigated. In these studies, only actinonin demonstrated a positive effect on the stability of all radiopeptides. In contrast, phosphoramidon yielded variable results, and neither captopril nor E−64 showed a significant stabilizing effect.&lt;/div&gt;&lt;div&gt;Consequently, the effect of actinonin administration on the &lt;em&gt;in vivo&lt;/em&gt; PET/CT imaging results of the most promising ligand [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-[Lys&lt;sup&gt;4&lt;/sup&gt;(N&lt;sub&gt;ε&lt;/sub&gt;-NODA-GA)]BVD15 ([&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-&lt;strong&gt;2&lt;/strong&gt;) was investigated in a T47D tumor-bearing xenograft mouse model, followed by &lt;em&gt;ex vivo&lt;/em&gt; biodistribution studies. In these experiments, the administration of 250 μg actinonin resulted in a significantly increased uptake of [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-&lt;strong&gt;2&lt;/strong&gt; in the T47D tumor (5.9 ± 1.0 % ID/g (with actinonin) instead of 3.1 ± 0.9 % ID/g (without actinonin) at 2h p.i.), and an increase in tumor-to-muscle ratios from 1.8 to 4.0 upon co-administration of the inhibitor.&lt;/div&gt;&lt;div&gt;The results impressively demonstrate the positive influence of actinonin on the &lt;em&gt;in vivo&lt;/em&gt; stability of the NPY(Y&lt;sub&gt;1&lt;/sub&gt;)R-specific radiopeptide [&lt;sup&gt;68&lt;/sup&gt;","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100223"},"PeriodicalIF":0.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer effect of new cyclocoumarol derivatives","authors":"Racha Karaky ,&nbsp;Joumana Al-Akhdar ,&nbsp;Fatima Saab ,&nbsp;Batoul Rostom ,&nbsp;Wassim Shebaby ,&nbsp;Mohamed Mroueh ,&nbsp;Mona Diab-Assaf ,&nbsp;Issam Kassab ,&nbsp;Maité Sylla-Iyarreta Veitia","doi":"10.1016/j.ejmcr.2024.100220","DOIUrl":"10.1016/j.ejmcr.2024.100220","url":null,"abstract":"<div><div>Coumarins have demonstrated a broad spectrum of pharmacological activities, including significant anticancer properties. Recently, a series of cyclocoumarol derivatives, a pyranocoumarin known for its anticoagulant and anti-inflammatory effects, have been synthesized and shown to have a selective inhibitory effect on cyclooxygenase-2 (COX-2). In this study, we evaluated the anticancer effects of these cyclocoumarol derivatives for the first time. We tested their antiproliferative effects on several human cancer cell lines, including MDAMB231, A549, MCF7, SF268, HCT116, HeLa, and Jurkat. The MTT assay revealed that the methylated cyclocoumarol derivative, 2-methoxy-2-methyl-(1-(p-tolyl))-3,4-dihydropyrano [3,2-c] chromen-5(2H)-one, <strong>5b</strong> exhibited the most potent antiproliferative activity, particularly against MDAMB231 cells. Further investigations demonstrated that <strong>5b</strong> induced apoptosis in MDAMB231 cells via the mitochondrial pathway, as indicated by increased Bax and decreased Bcl2 levels, along with caspase-3 activation and PARP cleavage. Additionally, compound <strong>5b</strong> significantly inhibited the clonogenic potential of MCF7 cells and reduced the migration capacity of MDAMB231, SF268, and A549 cells. These findings suggest that <strong>5b</strong> is a promising lead compound for developing new anticancer agents, with the potential for chemical optimization to enhance its efficacy.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100220"},"PeriodicalIF":0.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}