Journal of Heterocyclic Chemistry最新文献

{"title":"Synthesis and Antitumor Activity of New Metronidazole-Linked Thiophene or Pyrazole Analogues","authors":"Yasir Jabbar Abbas Altamimi,&nbsp;Heshmatollah Alinezhad,&nbsp;Mahmood Tajbakhsh,&nbsp;Hatem E. Gaffer","doi":"10.1002/jhet.70002","DOIUrl":"https://doi.org/10.1002/jhet.70002","url":null,"abstract":"<div>\u0000 \u0000 <p>A series of metronidazole hybridized with various substituted thiophene and/or pyrazole derivatives was synthesized, and their structure was identified by using spectroscopic methods, including IR, MS, ¹H NMR, and ¹³C NMR. The created metronidazole-thiophene and metronidazole-pyrazole hybrids were investigated toward dissimilar cell lines, HCT-116, PC3, HepG2, and MCF-7, as well as the WI38 standard cell line, and the results showed a good effectiveness toward the MCF-7 cell line in comparison to Dox. as a control. Meanwhile, metronidazole hybrids <b>14a-d</b> containing an amino-pyrazole moiety demonstrated strong anticancer activity against MCF-7 with IC₅₀ ranging from 5.18 ± 0.39 to 11.51 ± 0.33 μM while Dox exhibited an IC₅₀ of 1.36 ± 0.18 μM. The structure–activity relationship of synthesized metronidazole hybrids was examined, and an intriguing remark was observed in terms of anticancer activity, particularly against the MCF-7 cell line. The molecular docking method was employed to analyze how the target protein (PdB: 3U9W, human leukotriene A-4 hydrolase, LA4H) interacts with the synthesized molecules.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 8","pages":"653-666"},"PeriodicalIF":2.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861787","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}

{"title":"Polycyclic Dicationic Heteroaromatic Compounds From One-Step Multiple Condensation Reactions: Synthesis and Reactivity","authors":"Paola Sánchez-Portillo,&nbsp;Alan Rivera-Beltrán,&nbsp;Luis Alejandro Suastegui-Blancas,&nbsp;Jacobo Rivera-Segura,&nbsp;Victor Barba","doi":"10.1002/jhet.70027","DOIUrl":"https://doi.org/10.1002/jhet.70027","url":null,"abstract":"<div>\u0000 \u0000 <p>The synthesis of nitrogen-containing polycyclic aromatic compounds (NPACs) from simple condensation reactions is described. 2,6-diformylpyridine was reacted with aniline derivatives in the presence of sulfuric acid as catalyst, giving rise to the formation of NPACs in one-step reaction. Aniline and derivatives, including <i>p</i>-Cl and <i>m</i>-B(OH)₂ substituents, have been used as starting materials; in all three cases, the main core of the resulting compounds includes a dicationic five-fused cyclic system. The core of the whole structure is related to the polycyclic aromatic hydrocarbon dihydrocyclopenta[hi]aceanthrylene. The absorption bands are similar for all three cases; the small variations in the absorption coefficient were associated with the pyridyl substituent. The Lewis acid behavior of the boronic acid groups was explored by titration with Ca(OH)₂. In addition, the reactivity of the boronic acid groups was proven with aminodiols. N–B dative bonds favor the formation of five-membered bicyclic structures.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 8","pages":"606-612"},"PeriodicalIF":2.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861785","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}

{"title":"[1,2,4]Triazolo[3,4-b][1,3,4]Thiadiazin-3-Yl)methyl)pyrimidin-4(3H)-One Derivatives as New Therapeutic Candidates as COX-II Inhibitors: Green Synthetic Approach and In Silico Studies","authors":"Kevalsinh B. Rathod,&nbsp;Mehul N. Ramoliya,&nbsp;Kartik D. Ladva,&nbsp;Mahesh M. Savant","doi":"10.1002/jhet.70017","DOIUrl":"https://doi.org/10.1002/jhet.70017","url":null,"abstract":"<div>\u0000 \u0000 <p>This study presented a systematic synthesis of [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazin-3-yl)methyl)-6-methylpyrimidin-4(3<i>H</i>)-one derivative <b>(9a-j)</b> through three distinct methodologies: a traditional multistep approach, a two-step solid-phase synthesis, and a one-step green synthesis. The green synthesis demonstrated superior atom economy, minimal impurities, and adherence to sustainability principles. The synthesized compounds were evaluated for cyclooxygenase (COX) inhibition, with <b>9e</b> showing the highest COX-II selectivity (SI = 17.10), supported by in vitro and <i>in silico</i> analyses. Structure–activity relationships revealed the impact of electron-withdrawing groups on binding affinity. This work highlighted an efficient, environmentally conscious approach to creating pharmacologically relevant heterocycles.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 8","pages":"596-605"},"PeriodicalIF":2.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861784","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}

{"title":"Copper-Free Sonogashira Coupling of Coumarin Fluorosulfates in Water: A Modified Approach for the Synthesis of Novel Alkynyl Coumarin Derivatives","authors":"M. Rajini,&nbsp;Venkatachalam Munusamy,&nbsp;Muthipeedika Nibin Joy,&nbsp;Grigory V. Zyryanov","doi":"10.1002/jhet.70015","DOIUrl":"https://doi.org/10.1002/jhet.70015","url":null,"abstract":"<div>\u0000 \u0000 <p>A modified, atom-economical, and ecofriendly approach developed for synthesizing an array of alkynyl coumarin derivatives by exploring the copper-free Sonogashira coupling reaction is reported herein. The usage of water as a solvent, along with the utilization of coumarin fluorosulfate as an atom-economical electrophilic coupling partner, demonstrates the synthetic utility of this modified methodology. The superiority of coumarin fluorosulfate over other pseudohalide-based leaving groups has been realized by performing a comparative study at a later stage. The environmental friendliness of our modified synthetic protocol has been realized by calculating the E-factor for the formation of products at the final stage.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 8","pages":"568-574"},"PeriodicalIF":2.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861795","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}

{"title":"Novel Triazole-Based Heterocycles Outperform Doxorubicin: Design, Synthesis, and Biological Evaluation as MMP13-Targeting Anticancer Agents","authors":"Samar E. Mahmoud,&nbsp;Ahmed A. Fadda,&nbsp;Ehab Abdel-Latif,&nbsp;Mohamed R. Elmorsy","doi":"10.1002/jhet.70016","DOIUrl":"https://doi.org/10.1002/jhet.70016","url":null,"abstract":"<div>\u0000 \u0000 <p>A series of novel triazole-fused heterocyclic compounds was prepared and evaluated for their anticancer potential. The target molecules (<b>3</b>, <b>5</b>, <b>7</b>, <b>9</b>, <b>11</b>, <b>13</b>, <b>15</b>, <b>17</b>, <b>19</b>, <b>21</b>, and <b>23</b>) were prepared through strategic cyclization reactions starting from the key intermediate 4-(bromoacetyl)-5-methyl-1-phenyltriazole (<b>1</b>). These triazole-containing scaffolds included imidazobenzimidazoles, imidazobenzothiazoles, imidazotriazoles, imidazothiadiazoles, triazolyl-imidazopyridines, triazolyl-quinoxalines, and triazolyl-benzothiazines. The chemical structures of the synthesized compounds were thoroughly characterized using spectroscopic methods. Evaluation of their in vitro anticancer activities against prostate (PC3) and breast (MDA-MB-231) cancer cell lines detected that 6,8-dichloro-2-(5-methyl-1-phenyl-1<i>H</i>-1,2,3-triazol-4-yl)imidazo[1,2-<i>a</i>]pyridine (<b>13</b>) and 3-(5-methyl-1-phenyl-1<i>H</i>-1,2,3-triazol-4-yl)-4<i>H</i>-benzo[<i>b</i>][1,4]thiazine (<b>17</b>) exhibited the most potent cytotoxicity, outperforming the standard drug doxorubicin. Notably, triazolyl-imidazopyridine compound <b>13</b> displayed significantly lower IC₅₀ values of 5.86 and 23.07 μM against PC3 and MDA-MB-231 cells, respectively, compared to doxorubicin. In silico ADME property predictions were also performed to assess the drug-likeness of these triazole-based heterocycles. Target prediction identified MMP13 as a major target. Further mechanistic insights were gained through molecular docking investigations, which elucidated the binding interactions of the active triazole compounds <b>13</b> and <b>17</b> with the protein target MMP13. Molecular dynamics simulations over 100 ns provided evidence of the stability and flexibility of the docked complexes. The mechanism of the potent compound <b>13</b> was validated experimentally by wound healing inhibition and suppression of the expression of MMP13 in PC3 culture media.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 8","pages":"575-595"},"PeriodicalIF":2.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861796","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}

{"title":"Visible-Light Induced Rose Bengal Photocatalyzed One-Pot Environmentally Sustainable Multicomponent Synthesis of Substituted Pyrazolo[3,4-b]Quinolin-5-Ones","authors":"Vishwa K. Patel,&nbsp;Divyani P. Patel,&nbsp;Satish Kumar Singh","doi":"10.1002/jhet.70007","DOIUrl":"https://doi.org/10.1002/jhet.70007","url":null,"abstract":"<div>\u0000 \u0000 <p>In this study, we report the first sustainable and efficient visible-light-induced one-pot multicomponent synthesis of substituted pyrazolo[3,4-<i>b</i>]quinolin-5-ones, employing rose bengal (RB) as a photocatalyst. The innovative method integrates green chemistry principles, leveraging the eco-friendly and cost-effective properties of RB, a versatile organic dye, under mild reaction conditions. Mechanistic studies suggest that the process involves single-electron transfer (SET) reactions facilitated by the photocatalyst upon visible-light activation. This approach underscores the synergy between visible-light photochemistry and multicomponent reactions, delivering a robust, atom-economical strategy for synthesizing biologically and industrially significant heterocycles, with potential applications in medicinal chemistry and beyond.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 8","pages":"562-567"},"PeriodicalIF":2.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861708","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}

{"title":"Copper-Catalyzed Synthesis of Pyrazolo[4′,5′:4,5]Pyrimido[1,2-c]Quinazolines via Ullmann, Decarboxylation and Oxidative Coupled Dehydrogenation","authors":"Yun-Xiang Zhou,&nbsp;Lu-Yi Wang,&nbsp;Wei-Dong Jiang,&nbsp;Lai-Long Mu,&nbsp;Lan-Lan Lv,&nbsp;Xiang-Shan Wang","doi":"10.1002/jhet.70010","DOIUrl":"https://doi.org/10.1002/jhet.70010","url":null,"abstract":"<div>\u0000 \u0000 <p>5-(2-Bromophenyl)-1-methyl-3-propyl-1,6-dihydro-7<i>H</i>-pyrazolo[4,3-<i>d</i>] pyrimidin-7-one was used as a reactant to react with <span>l</span>-proline or pipecolic acid catalyzed by CuI, and it underwent consecutive Ullmann coupling, decarboxylation, and oxidative coupled dehydrogenation to give pyrazolo[4′,3′:4,5] pyrimido[1,2-<i>c</i>] pyrrolo/pyrido [1,2-<i>a</i>]quinazolin-13(12<i>H</i>)-ones in good yields.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 8","pages":"554-561"},"PeriodicalIF":2.0,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861707","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}

{"title":"Synthesis of Fluorescent 2-(Pyrano[3,2-c]chromene-5-yl)Acetic Acids From Chromone-Containing Acrylic Acids","authors":"Sergey V. Efimov,&nbsp;Nikita M. Chernov,&nbsp;Maxim S. Panov,&nbsp;Dmitrii M. Nikolaev,&nbsp;Mikhail N. Ryazantsev,&nbsp;Roman V. Shutov,&nbsp;Igor P. Yakovlev","doi":"10.1002/jhet.70008","DOIUrl":"https://doi.org/10.1002/jhet.70008","url":null,"abstract":"<div>\u0000 \u0000 <p>We have developed a convenient method for the synthesis of 2-(pyrano[3,2-<i>c</i>]chromen-5-yl)acetic acids and their derivatives. The synthetic approach is based on the ANRORC reaction of chromone-containing acrylic acids and ethyl cyanoacetate. The features of the method are (a) simple reaction conditions (ethanol, 20°C–25°C, triethylamine as catalyst), (b) non-chromatographic isolation of products, and (c) high yields (up to 95%). The resulting pyrano[3,2-<i>c</i>]chromenes have intense fluorescence in the yellow-green region of the spectrum (492–554 nm) and demonstrate large Stokes shifts (up to 6300 cm⁻¹).</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 8","pages":"546-553"},"PeriodicalIF":2.0,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861706","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}

{"title":"Synthesis of Novel 1,2,3-Triazole Derivatives via Click Chemistry and Evaluation of Their Antifungal Activity","authors":"Haidong Zhang,&nbsp;Fei Xie,&nbsp;Yumeng Hao,&nbsp;Yongsheng Jin,&nbsp;Dazhi Zhang,&nbsp;Guanghui Ni,&nbsp;Canhui Zheng,&nbsp;Yuanying Jiang,&nbsp;Shichong Yu","doi":"10.1002/jhet.70006","DOIUrl":"https://doi.org/10.1002/jhet.70006","url":null,"abstract":"<div>\u0000 \u0000 <p>Due to clinical demands, there remains a need for new triazole antifungal compounds to broaden the antifungal spectrum and enhance therapeutic efficacy. In this paper, we have developed an effective method for obtaining triazole compounds with 1,2,3-triazole groups introduced into their side chains via click chemistry, targeting the active site of cytochrome P450 14α-demethylase (CYP51). In vitro antifungal activity tests of the title compounds against three human pathogenic fungi demonstrated that this class of compounds exhibited good antifungal activity. Notably, compound <b>2d</b> exhibits superior antifungal activity compared to fluconazole against \u0000 <i>Candida albicans</i>\u0000 SC5314 (with the MIC value of ≤ 0.125 μg/mL) and \u0000 <i>Cryptococcus neoformans</i>\u0000 32609 (with the MIC value of 2 μg/mL), meriting further investigation. Molecular docking results indicated that the introduced 1,2,3-triazole rings in the side chains formed π–π stacking interactions with Tyr118 of CYP51, along with additional hydrogen bonds. This paper provides a method for rapidly modifying the side chains of triazole antifungal drugs in the future to obtain compounds with further enhanced activity.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 8","pages":"535-545"},"PeriodicalIF":2.0,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861705","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}

{"title":"Ultrasound-Assisted Utility of 1,2,4-Triazole as a Multisite-Sequential Scaffold to Construct Different Heterocycles, Accredited by Molecular Modeling and Electrochemical Studies","authors":"Eslam A. Ghaith,&nbsp;A. B. Abdallah,&nbsp;Aya Atef El-Sawi,&nbsp;Ghada G. El-Bana","doi":"10.1002/jhet.70003","DOIUrl":"https://doi.org/10.1002/jhet.70003","url":null,"abstract":"<div>\u0000 \u0000 <p>In the present work, the tail approach chemical reactivity of 4-amino-5-hydrazinyl-4<i>H</i>-1,2,4-triazole-3-thiol (<b>1</b>) with trade name purpald towards various carbonyl groups is exploited to synthesize heterocyclic molecules such as triazine, tetrazine, and thiadiazepine fused and integrated with the triazole scaffold. The controlled and effective reaction of the site-selective hydrazinyl group proceeds smoothly in acidified methanol at ambient conditions under ultrasonic irradiation as an eco-friendly method enhancing product purity with easier work-up in a shorter reaction time compared with conventional methods. It was observed that the final products were obtained in high yields (89%–99%) in 0.25–5 min by the sonochemical method versus 68%–94% by the conventional method in a time range of 2–35 min. Further to this, the economic yields (YE) of the synthesized compounds were calculated to confirm and compare the efficiency of the two different synthetic methods. Moreover, computational studies were conducted to clarify the regiodivergence of tautomeric forms of 1,2,4-triazol-3-yl-hydrazineylidene-6-hydroxypyrimidine-2,4(3<i>H</i>,5<i>H</i>)-dione <b>26</b> and elucidate the most optimized tautomer via using density functional theory (DFT). Furthermore, most of the synthesized heterocyclic systems <b>26</b>, <b>5</b>, <b>29</b>, <b>6</b>, <b>22</b>, and <b>24</b> in the same order, which were fabricated by the ultrasonication technique, showed excellent conductivity and low resistivity than other investigated scaffolds <b>3</b>, <b>8</b>, <b>11</b>, <b>12</b>, <b>14</b>, <b>16</b>, <b>17</b>, <b>19</b>, and <b>21</b>, depending on electrochemical impedance spectroscopy measurements.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"62 8","pages":"505-517"},"PeriodicalIF":2.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861641","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}