The sea hare, scientifically known as Aplysia argus, is the focus of considerable research interest owing to its unique halogenated metabolites that may have vast potential in the fields of medicine and pharmaceuticals. This paper reports the isolation of a new laurane-type sesquiterpene, 10-bromoisolaurinsiol (1), and a new halogenated C15 acetogenin (2), along with several known halogenated secondary metabolites from the sea hare Aplysia argus. Their structures and relative stereochemistries were established through comprehensive 1D and 2D NMR analyses. Fourteen compounds, some of which were novel, were evaluated for their cytotoxic effects against S1T cells (a cancer cell line derived from adult T-cell leukemia patients) and their potential as SARS-CoV-2 main protease inhibitors.
{"title":"Isolation, characterization, and biological activities of halogenated sesquiterpenes and C15 acetogenins from the Okinawan sea hare, Aplysia argus","authors":"Ryunosuke Nakamura , Koushi Matsuyama , Naomichi Arima , Fumito Tani , Satoaki Onitsuka , Hiroaki Okamura , Tetsuo Iwagawa , Masayuki Sudoh , Toshiyuki Hamada","doi":"10.1016/j.tet.2025.134588","DOIUrl":"10.1016/j.tet.2025.134588","url":null,"abstract":"<div><div>The sea hare, scientifically known as <em>Aplysia argus</em>, is the focus of considerable research interest owing to its unique halogenated metabolites that may have vast potential in the fields of medicine and pharmaceuticals. This paper reports the isolation of a new laurane-type sesquiterpene, 10-bromoisolaurinsiol (<strong>1</strong>), and a new halogenated C<sub>15</sub> acetogenin (<strong>2</strong>), along with several known halogenated secondary metabolites from the sea hare <em>Aplysia argus</em>. Their structures and relative stereochemistries were established through comprehensive 1D and 2D NMR analyses. Fourteen compounds, some of which were novel, were evaluated for their cytotoxic effects against S1T cells (a cancer cell line derived from adult T-cell leukemia patients) and their potential as SARS-CoV-2 main protease inhibitors.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"178 ","pages":"Article 134588"},"PeriodicalIF":2.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The utilisation of photosensitive cross-linked porous organic polymers doped with Au nanoparticles (NPs) (PDI-BT-5-Au) has proven successful as a remarkably effective photocatalyst for the aerobic oxidation of phenylboronic acid to phenol, utilising O2 under mild conditions. Furthermore, this research underscores the promise of Au NPs-enhanced cross-linked porous organic polymers as proficient, recyclable heterogeneous photocatalysts for organic transformations.
{"title":"Gold nanoparticle-enhanced cross-linked porous organic polymer photocatalysts for visible light-driven oxidation of phenylboronic acid","authors":"Xin Liu, Jiaxi Cai, Qiaoya Wang, Haixia Song, Aizhao Pan, Mingyou Hu","doi":"10.1016/j.tet.2025.134585","DOIUrl":"10.1016/j.tet.2025.134585","url":null,"abstract":"<div><div>The utilisation of photosensitive cross-linked porous organic polymers doped with Au nanoparticles (NPs) (PDI-BT-5-Au) has proven successful as a remarkably effective photocatalyst for the aerobic oxidation of phenylboronic acid to phenol, utilising O<sub>2</sub> under mild conditions. Furthermore, this research underscores the promise of Au NPs-enhanced cross-linked porous organic polymers as proficient, recyclable heterogeneous photocatalysts for organic transformations.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"177 ","pages":"Article 134585"},"PeriodicalIF":2.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-10DOI: 10.1016/j.tet.2025.134584
Qian Wang , Yue Wang , Er-Qing Li
In this work, we report the [2 + 1] cycloaddition reaction between electron-deficient conjugated dienes and sulfur ylides under catalyst-free and base-free conditions. The method provides an efficient pathway for constructing cyclopropane frameworks. This protocol exhibits excellent regioselectivity, good yields, and broad functional group tolerance. Furthermore, the potential applications of this approach are demonstrated through gram-scale reactions and further synthetic transformations.
{"title":"Catalyst-free [2 + 1] annulations of conjugated dienes and sulfur Ylides: Synthesis of cyclopropane derivatives","authors":"Qian Wang , Yue Wang , Er-Qing Li","doi":"10.1016/j.tet.2025.134584","DOIUrl":"10.1016/j.tet.2025.134584","url":null,"abstract":"<div><div>In this work, we report the [2 + 1] cycloaddition reaction between electron-deficient conjugated dienes and sulfur ylides under catalyst-free and base-free conditions. The method provides an efficient pathway for constructing cyclopropane frameworks. This protocol exhibits excellent regioselectivity, good yields, and broad functional group tolerance. Furthermore, the potential applications of this approach are demonstrated through gram-scale reactions and further synthetic transformations.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"177 ","pages":"Article 134584"},"PeriodicalIF":2.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this study, the synthesis of new enaminone derivatives via a three-component reaction of active methylene compounds, triethyl orthoformate, and aniline derivatives, in the presence of cerium oxide nanoparticles as an active catalyst, under solvent-free conditions has been developed. Cerium oxide nanoparticles were prepared using the aqueous extract of Salvadora persica as a green and environmentally friendly method. The effect of different parameters including solvent, reaction temperature, catalyst type, and catalyst amount was studied to achieve optimized reaction conditions. Cerium oxide nanoparticles have shown a higher yield than other catalysts such as Fe2O3, lactic acid, NaOAc, ZnCl2, nano-MgO, and nano-ZnO. The enaminone derivatives were synthesized in high to excellent yields with this protocol.
{"title":"Synthesis of new enaminone derivatives and studying the one-pot three-component reaction of anilines, triethyl orthoformate, and active methylene compounds using CeO2 nanoparticles as a catalyzing","authors":"Arezoo Sardashti-Birjandi, Ebrahim Mollashahi, Malek Taher Maghsoodlou","doi":"10.1016/j.tet.2025.134577","DOIUrl":"10.1016/j.tet.2025.134577","url":null,"abstract":"<div><div>In this study, the synthesis of new enaminone derivatives via a three-component reaction of active methylene compounds, triethyl orthoformate, and aniline derivatives, in the presence of cerium oxide nanoparticles as an active catalyst, under solvent-free conditions has been developed. Cerium oxide nanoparticles were prepared using the aqueous extract of <em>Salvadora persica</em> as a green and environmentally friendly method. The effect of different parameters including solvent, reaction temperature, catalyst type, and catalyst amount was studied to achieve optimized reaction conditions. Cerium oxide nanoparticles have shown a higher yield than other catalysts such as Fe<sub>2</sub>O<sub>3</sub>, lactic acid, NaOAc, ZnCl<sub>2</sub>, nano-MgO, and nano-ZnO. The enaminone derivatives were synthesized in high to excellent yields with this protocol.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"177 ","pages":"Article 134577"},"PeriodicalIF":2.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-05DOI: 10.1016/j.tet.2025.134545
Li-Jun Li, Xin-Yue Li, Jin Zhang, Hong Li, Qiang-Wei Fan, Yang Li
The presence of trifluoromethyl in the drug molecule can effectively improve its lipophilicity, absorbability, and metabolic stability. Therefore, the introduction of trifluoromethyl in organic molecules has attracted widespread attention. In recent years, the trifluoromethylation of olefins has been developed rapidly. In this paper, various synthesis methods and reaction mechanisms of trifluoromethylated olefins in recent years are reviewed from the perspectives of transition metal (Cu, Fe, Pd, Ni) catalysis and photocatalysis and free radical reactions.
{"title":"Progress in trifluoromethylation reaction of olefins","authors":"Li-Jun Li, Xin-Yue Li, Jin Zhang, Hong Li, Qiang-Wei Fan, Yang Li","doi":"10.1016/j.tet.2025.134545","DOIUrl":"10.1016/j.tet.2025.134545","url":null,"abstract":"<div><div>The presence of trifluoromethyl in the drug molecule can effectively improve its lipophilicity, absorbability, and metabolic stability. Therefore, the introduction of trifluoromethyl in organic molecules has attracted widespread attention. In recent years, the trifluoromethylation of olefins has been developed rapidly. In this paper, various synthesis methods and reaction mechanisms of trifluoromethylated olefins in recent years are reviewed from the perspectives of transition metal (Cu, Fe, Pd, Ni) catalysis and photocatalysis and free radical reactions.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"177 ","pages":"Article 134545"},"PeriodicalIF":2.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-03DOI: 10.1016/j.tet.2025.134569
Ali Nasirpour, Zarrin Ghasemi
An efficient protocol is disclosed for the synthesis of benzimidazo[1,2-c]quinazolin-6(5H)-ones utilizing an atom-economical C–H functionalization method. Copper-mediated isocyanatation of the aryl ring of the prepared 2-arylbenzimidazole derivatives, followed with intramolecular cyclization reaction resulted in the desired products. We diversified and purified the products without chromatography.
{"title":"Synthesis of benzimidazo[1,2-c]quinazolin-6(5H)-one derivatives via copper-mediated C–H isocyanatation of 2-arylbenzimidazoles","authors":"Ali Nasirpour, Zarrin Ghasemi","doi":"10.1016/j.tet.2025.134569","DOIUrl":"10.1016/j.tet.2025.134569","url":null,"abstract":"<div><div>An efficient protocol is disclosed for the synthesis of benzimidazo[1,2-<em>c</em>]quinazolin-6(5<em>H</em>)-ones utilizing an atom-economical C–H functionalization method. Copper-mediated isocyanatation of the aryl ring of the prepared 2-arylbenzimidazole derivatives, followed with intramolecular cyclization reaction resulted in the desired products. We diversified and purified the products without chromatography.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"177 ","pages":"Article 134569"},"PeriodicalIF":2.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.tet.2025.134567
Xian-Fei Deng, Yan-Jun Chen, Li-Yu Yi, Ju Huang
New bulky N-heterocyclic carbene (NHC) palladium complexes {[Pd-PEPPSI-IPrtBuDBB]} were synthesized and characterized. The catalytic activity of the palladium complexes was evaluated via the direct C–N arylation of N-heteroaryl amines with aryl chlorides in aerobic conditions at 100 °C. Under the optimal conditions, 2 mol% of the bulky palladium was found to be very efficient and produced the desired cross-coupling products in high yields.
{"title":"New NHC–Pd complexes bearing bulky steric hindrance: Synthesis and catalytic activity in the Heteroaryl–Heteroaryl Buchwald–Hartwig amination reaction","authors":"Xian-Fei Deng, Yan-Jun Chen, Li-Yu Yi, Ju Huang","doi":"10.1016/j.tet.2025.134567","DOIUrl":"10.1016/j.tet.2025.134567","url":null,"abstract":"<div><div>New bulky N-heterocyclic carbene (NHC) palladium complexes {[Pd-PEPPSI-IPr<sup>tBuDBB</sup>]} were synthesized and characterized. The catalytic activity of the palladium complexes was evaluated via the direct C–N arylation of N-heteroaryl amines with aryl chlorides in aerobic conditions at 100 °C. Under the optimal conditions, 2 mol% of the bulky palladium was found to be very efficient and produced the desired cross-coupling products in high yields.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"177 ","pages":"Article 134567"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This research work introduces a pioneering strategy for harnessing the potential of expired streptomycin sulfate as its copper chelate to catalyze the synthesis of biologically important 1,4-disubstituted-1,2,3-triazoles efficiently. The efficacy of this catalyst is showcased by the sonochemical 1,3-dipolar cycloaddition process, yielding 1,4-disubstituted-1,2,3-triazoles at 40 °C using a promotor ligand l-phenylalanine within 30 min in >90 % yield in aqueous media with high purity. The biocompatible promoter ligand assists the STR Cu chelate to enhance the reaction rate by stabilizing the Cu(I) oxidation state and preventing its undesirable disproportionation, thus increasing the yield of the intended product. The synthesized catalyst demonstrates extensive substrate compatibility and works equally well with precursors containing both electron donating and withdrawing groups (4–25). Additionally, all the synthesized compounds, as well as the catalyst, have been duly characterized by the usual analytical and spectroscopic techniques. Furthermore, the catalyst could be reused up to four cycles without a significant reduction in its catalytic performance.
这项研究工作介绍了一种开创性的策略，利用过期硫酸链霉素作为其铜螯合物的潜力，高效催化合成具有重要生物意义的 1,4-二取代-1,2,3-三唑。这种催化剂的功效体现在声化学 1,3 双极环加成过程中，使用促进配体苯丙氨酸，在水介质中于 40 °C 下 30 分钟内生成 1,4-二取代-1,2,3-三唑，收率达 90%，纯度高。生物相容性促进配体通过稳定 Cu（I）的氧化态并防止其发生不应有的歧化反应，协助 STR Cu 螯合物提高反应速率，从而提高了预期产物的产率。合成的催化剂具有广泛的底物兼容性，对含有电子供体和电子汲取基团（4-25）的前体同样有效。此外，所有合成的化合物和催化剂都已通过常用的分析和光谱技术进行了适当的表征。此外，催化剂可重复使用四次，而其催化性能不会明显降低。
{"title":"Sonochemically synthesized copper chelate from expired streptomycin sulfate as a sustainable catalyst for green synthesis of 1,4-disubstituted triazoles in aqueous medium","authors":"Neetu Mev , Yachana Jain , Lalita Yadav , Priya Sharma , Madhu Agarwal , Ragini Gupta","doi":"10.1016/j.tet.2025.134564","DOIUrl":"10.1016/j.tet.2025.134564","url":null,"abstract":"<div><div>This research work introduces a pioneering strategy for harnessing the potential of expired streptomycin sulfate as its copper chelate to catalyze the synthesis of biologically important 1,4-disubstituted-1,2,3-triazoles efficiently. The efficacy of this catalyst is showcased by the sonochemical 1,3-dipolar cycloaddition process, yielding 1,4-disubstituted-1,2,3-triazoles at 40 °C using a promotor ligand <span>l</span>-phenylalanine within 30 min in >90 % yield in aqueous media with high purity. The biocompatible promoter ligand assists the STR Cu chelate to enhance the reaction rate by stabilizing the Cu(I) oxidation state and preventing its undesirable disproportionation, thus increasing the yield of the intended product. The synthesized catalyst demonstrates extensive substrate compatibility and works equally well with precursors containing both electron donating and withdrawing groups (<strong>4–25</strong>). Additionally, all the synthesized compounds, as well as the catalyst, have been duly characterized by the usual analytical and spectroscopic techniques. Furthermore, the catalyst could be reused up to four cycles without a significant reduction in its catalytic performance.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"177 ","pages":"Article 134564"},"PeriodicalIF":2.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-28DOI: 10.1016/j.tet.2025.134563
Xinglei He , Xiaobin Zhu , Luyao Wang , Jingheng Li , Chunlong Yu , Ke-Yin Ye
Vicinal diamines are an important structural motif that has been widely used in biological, medicinal, and materials science. Transition-metal-catalyzed diazidation of alkene is a straightforward and efficient approach for vicinal diamines, which are unfavorably associated with excess oxidants and limited substrate scope for electron-deficient alkenes. Herein we report an electrocatalytic diazidation of alkenes with the electrode coated by Cu nanoparticles pyrolyzed from Cu(salen)-based metal-organic framework. This strategy is compatible with various alkenes including those electro-deficient ones. Remarkably, the modified electrode maintains high electrocatalytic activity for diazidation even after 15 cycles.
{"title":"Electrocatalytic diazidation of alkenes with modified electrodes coated by Cu nanoparticles","authors":"Xinglei He , Xiaobin Zhu , Luyao Wang , Jingheng Li , Chunlong Yu , Ke-Yin Ye","doi":"10.1016/j.tet.2025.134563","DOIUrl":"10.1016/j.tet.2025.134563","url":null,"abstract":"<div><div>Vicinal diamines are an important structural motif that has been widely used in biological, medicinal, and materials science. Transition-metal-catalyzed diazidation of alkene is a straightforward and efficient approach for vicinal diamines, which are unfavorably associated with excess oxidants and limited substrate scope for electron-deficient alkenes. Herein we report an electrocatalytic diazidation of alkenes with the electrode coated by Cu nanoparticles pyrolyzed from Cu(salen)-based metal-organic framework. This strategy is compatible with various alkenes including those electro-deficient ones. Remarkably, the modified electrode maintains high electrocatalytic activity for diazidation even after 15 cycles.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"176 ","pages":"Article 134563"},"PeriodicalIF":2.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-28DOI: 10.1016/j.tet.2025.134557
Mirna T. Helmy, Mohamed A. Mohamed Teleb, Demiana H. Hanna, Mohamed W. El-Maadawy, Hamdi M. Hassaneen, Monica G. Kamel
Utility of the precursors 3-aryl-4-imino-1-phenylpyrazolo[3,4-d]pyrimidin-5-amines 4a-f and 3-aryl-4-hydrazineyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidines 5a-f in the synthesis of pyrazolo[3,4-d]pyrimidin-4-yl)hydrazono derivatives 10a-lvia reaction of the hydrazines 5a-f with each of pyruvic acid or ethyl pyruvate 9. Refluxing of the hydrazone derivatives 10a-l in N,N-dimethylformamide for 90 h afforded the corresponding 3-methyl-8-phenylpyrazolo-[3′,4':4,5]pyrimido[6,1-c][1,2,4]triazine derivatives 11a-f. The cytotoxic results showed that the compound 11a was the most effective in suppressing the growth of HeLa cancer cells when compared to all other prepared compounds, with the most effective IC50 value (3.46 ± 0.59 μg/mL) and no cytotoxic effects on normal human lung cells (WI-38). Moreover, the toxicity of the compound 11a against HeLa cells was confirmed by a significant increase in LDH levels in treated HeLa cells compared to untreated ones. Using annexin V/PI, treated HeLa cells with this IC50 value of compound 11a displayed a considerable increase in early and late apoptotic cells in comparison to control cells. Additionally, apoptosis induction in the compound 11a-treated cells was mediated through increased reactive oxygen species (ROS) production. Moreover, the compound 11a markedly decreased the levels of antioxidant enzymes, including GSH, CAT, and SOD, in treated HeLa cells relative to untreated cells. Finally, the compound 11a markedly raised the expression levels of cleaved caspase-3, which is the initiator of apoptosis. Overall, these findings indicate that the compound 11a triggers significant cytotoxicity in HeLa cell cancer cells in a dose-dependent manner, primarily via ROS-mediated cell death, possibly via the mitochondrial pathway. So, compound 11a can be used as a promising treatment option for HeLa cancer in humans. In addition, in silico modelling, including, bioavailability, ADMET analysis, molecular docking and molecular dynamics simulation was conducted to evaluate the drug-likeness of the novel compounds (10a-11f). Compound 11a exhibited a promising binding affinity and stability against the receptors affirming its ability to act as antitumor and antioxidant ligand.
{"title":"Convenient synthesis, characterization, evaluation and molecular docking of some new fused pyrazolo[3,4-d]pyrimidine derivatives and 3-methyl-8 phenylpyrazolo[3′,4':4,5]pyrimido[6,1-c][1,2,4]triazines against HeLa cancer cells","authors":"Mirna T. Helmy, Mohamed A. Mohamed Teleb, Demiana H. Hanna, Mohamed W. El-Maadawy, Hamdi M. Hassaneen, Monica G. Kamel","doi":"10.1016/j.tet.2025.134557","DOIUrl":"10.1016/j.tet.2025.134557","url":null,"abstract":"<div><div>Utility of the precursors 3-aryl-4-imino-1-phenylpyrazolo[3,4-<em>d</em>]pyrimidin-5-amines <strong>4a-f</strong> and 3-aryl-4-hydrazineyl-1-phenyl-1<em>H</em>-pyrazolo[3,4-<em>d</em>]pyrimidines <strong>5a-f</strong> in the synthesis of pyrazolo[3,4-<em>d</em>]pyrimidin-4-yl)hydrazono derivatives <strong>10a-l</strong> <em>via</em> reaction of the hydrazines <strong>5a-f</strong> with each of pyruvic acid or ethyl pyruvate <strong>9</strong>. Refluxing of the hydrazone derivatives <strong>10a-l</strong> in <em>N</em>,<em>N</em>-dimethylformamide for 90 h afforded the corresponding 3-methyl-8-phenylpyrazolo-[3′,4':4,5]pyrimido[6,1-<em>c</em>][1,2,4]triazine derivatives <strong>11a-f</strong>. The cytotoxic results showed that the compound <strong>11a</strong> was the most effective in suppressing the growth of HeLa cancer cells when compared to all other prepared compounds, with the most effective IC<sub>50</sub> value (3.46 ± 0.59 μg/mL) and no cytotoxic effects on normal human lung cells (WI-38). Moreover, the toxicity of the compound <strong>11a</strong> against HeLa cells was confirmed by a significant increase in LDH levels in treated HeLa cells compared to untreated ones. Using annexin V/PI, treated HeLa cells with this IC<sub>50</sub> value of compound <strong>11a</strong> displayed a considerable increase in early and late apoptotic cells in comparison to control cells. Additionally, apoptosis induction in the compound <strong>11a</strong>-treated cells was mediated through increased reactive oxygen species (ROS) production. Moreover, the compound <strong>11a</strong> markedly decreased the levels of antioxidant enzymes, including GSH, CAT, and SOD, in treated HeLa cells relative to untreated cells. Finally, the compound <strong>11a</strong> markedly raised the expression levels of cleaved caspase-3, which is the initiator of apoptosis. Overall, these findings indicate that the compound <strong>11a</strong> triggers significant cytotoxicity in HeLa cell cancer cells in a dose-dependent manner, primarily <em>via</em> ROS-mediated cell death, possibly <em>via</em> the mitochondrial pathway. So, compound <strong>11a</strong> can be used as a promising treatment option for HeLa cancer in humans. In addition, <em>in silico</em> modelling, including, bioavailability, ADMET analysis, molecular docking and molecular dynamics simulation was conducted to evaluate the drug-likeness of the novel compounds (<strong>10a-11f</strong>). Compound <strong>11a</strong> exhibited a promising binding affinity and stability against the receptors affirming its ability to act as antitumor and antioxidant ligand.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"177 ","pages":"Article 134557"},"PeriodicalIF":2.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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