Polycyclic Aromatic Compounds最新文献

{"title":"Rational Design and Synthesis of 1,2,3-Triazole Incorporated Oxazolo[5,4-d] Pyrimidine Derivatives: In-Vitro Cytotoxicity and In-Silico Molecular Docking Simulations","authors":"Bajam Arun ,&nbsp;Manuri Brahmayya ,&nbsp;Reddymasu Sreenivasulu ,&nbsp;Dasari Sravani ,&nbsp;Suresh Dodda ,&nbsp;Ravi Kumar Kapavarapu ,&nbsp;Srimathi Krishnaswamy","doi":"10.1080/10406638.2025.2467956","DOIUrl":"10.1080/10406638.2025.2467956","url":null,"abstract":"<div><div>A new series of 1,2,3-Triazole incorporated oxazolo[5,4-<em>d</em>]pyrimidine derivatives <strong>24a-j</strong> were designed, synthesized and evaluated for their anticancer activity against MCF-7, A549, Colo-205, &amp; A2780 cell lines by using MTT reduction protocol with Etoposide as positive control. Among the screened derivatives, the compound <strong>24a</strong> showed potent anticancer activities against MCF-7, and A549 cell lines with IC₅₀ values of 0.11 ± 0.086 and 0.13 ± 0.094 µM, whereas another compound <strong>24h</strong> also showed potent anticancer activities against MCF-7, and A549 cell lines with IC₅₀ values of 0.18 ± 0.071 and 0.33 ± 0.067 µM. These activities are more potent than standard drug, Etoposide activities. Hence, these two derivatives are allowed for further investigations in cancer chemotherapy. This anticancer data also supported by the docking score of both the potent derivatives, <strong>24a</strong> and <strong>24h</strong>. The compounds <strong>24a</strong> and <strong>24h</strong> showed molecular interactions with human topoisomerase IIβ protein and having binding energies are −5.7 and −5.8 kcal/mole, respectively.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 8","pages":"Pages 1515-1535"},"PeriodicalIF":2.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195863","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":"Design, Synthesis, Antiproliferative Activity and In Silico Studies of 2-Oxo-1,2-Dihydroquinolin Derivatives","authors":"Eman A. E. El-Helw ,&nbsp;Eman A. Ghareeb ,&nbsp;Naglaa F. H. Mahmoud ,&nbsp;Eman A. El-Bordany ,&nbsp;Elsayed A. Soliman ,&nbsp;Khaled Abouzid ,&nbsp;Ahmed El-Khouly","doi":"10.1080/10406638.2025.2459212","DOIUrl":"10.1080/10406638.2025.2459212","url":null,"abstract":"<div><div>Quinolines have long been recognized as a versatile scaffold for the development of various bioactive compounds. In this context, a series of quinoline-based compounds were designed and synthesized using two key building block synthons: chalcone and thiocarbohydrazone derivatives. These compounds were synthesized following a design strategy inspired by the bis-indolyl maleimide-based PDK1 ATP-competitive inhibitor BIM-1. The final compounds were evaluated for their <em>in vitro</em> antiproliferative activity against MCF7 and HCT116 human cancer cell lines. Antiproliferative activity revealed that compound <strong>11</strong> displayed the best activity with IC₅₀ of 7.09 and 6.18 µM against HCT116 and MCF7 cell lines respectively. Furthermore, an in silico molecular docking study was performed on the PDK1 enzyme to investigate the binding affinity of compounds at the ATP-binding site. The docking analysis provided insight into the molecular interactions and binding modes of these compounds. Compound <strong>4</strong> showed the highest affinity with a binding score of −11 kcal/mol and an estimated Ki of 8.65 nM. Additionally, ADME (Absorption, Distribution, Metabolism, and Excretion) predictions indicated favorable drug-likeness and oral bioavailability profiles. This study aims to contribute to the development of promising anticancer agents.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 8","pages":"Pages 1431-1446"},"PeriodicalIF":2.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195858","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":"Revealing the Anti-Cancer Potential of 1,2,3-Triazole-Isonicotinate Derivatives Targeting EGFR Kinase Inhibition in MCF-7 Cancer Cells: Design, Synthesis, Biological Evaluation, and In Silico Studies","authors":"Asma Khalaf Alshamari ,&nbsp;Faiza I. A. Abdella ,&nbsp;Aljazi Abdullah AlRashidi ,&nbsp;Mona Zaheed Alshammari ,&nbsp;Hissah Khashman Alshammari ,&nbsp;Nuha Othman S. Alsaif ,&nbsp;Tamer El Malah","doi":"10.1080/10406638.2025.2490142","DOIUrl":"10.1080/10406638.2025.2490142","url":null,"abstract":"<div><div>Click chemistry was used to synthesize a new library of 1,2,3-triazole-isonicotinate derivatives <strong>8</strong>–<strong>13</strong> using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) between mono- or bis 2,6-ethynylisonicotinate <strong>3</strong>,<strong>4</strong>, and aromatic azides derivatives <strong>5</strong>–<strong>7</strong> with high yields (89–96%). These compounds were evaluated for their antiproliferative activity against hepatocellular carcinoma (Hep-G2), breast cancer (MCF-7), and colon cancer (HCT-116) cell lines, alongside a healthy non-cancerous skin fibroblast cell line (BJ-1). As compared with the reference drug, all new triazole-isonicotinate compounds have significantly greater cytotoxicity against colon and breast cancer cells, while compounds <strong>13</strong> and <strong>10</strong> have moderate cytotoxicity against liver cancer cells. The molecular docking study correlates the compound’s biological activity with its ability to establish stable interactions with protein-ligand complexes in the relevant biological targets. Compound <strong>13</strong> demonstrated a strong ability to induce apoptosis and cause cell cycle arrest in MCF-7 cells, along with significant inhibitory activity against the epidermal growth factor receptor (EGFR). These preliminary findings suggest that 1,2,3-triazole-isonicotinate derivatives, particularly compound <strong>13</strong>, hold potential as candidates for further investigation as anticancer agents for breast cancer treatment.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 8","pages":"Pages 1627-1648"},"PeriodicalIF":2.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195857","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, Tyrosinase Inhibition, Molecular Docking, and DFT Studies of Amide Derivatives of Fexofenadine","authors":"Muhammad Ayaz ,&nbsp;Aftab Alam ,&nbsp; Zainab ,&nbsp;Najeeb Ur Rehman ,&nbsp;Ahmed A. Elhenawy ,&nbsp;Masroor Kamal ,&nbsp;Muhammad Arif Lodhi ,&nbsp;Mumtaz Ali ,&nbsp;Abdul Latif ,&nbsp;Ahmed Al-Harrasi ,&nbsp;Manzoor Ahmad","doi":"10.1080/10406638.2025.2478141","DOIUrl":"10.1080/10406638.2025.2478141","url":null,"abstract":"<div><div>Tyrosinase is a core enzyme in the biosynthesis of melanin that is associated to dermatological illnesses, making its inhibition critical for cosmetics as well as therapeutic applications. To find new anti-browning and whitening agents, a series of twelve derivatives <strong>(1–12)</strong> of fexofenadine were prepared structurally deduced with the help of HR-ESIMS,¹H-, and ¹³C-NMR spectroscopy, and were screened for their <em>in vitro</em> tyrosinase inhibitory activity. All the synthesized products displayed excellent to moderate inhibitory activity except four compounds (<strong>1, 2, 6,</strong> and <strong>9</strong>) which were found non-active compared with standard kojic acid (IC₅₀ = 16.9 ± 1.30 µM). Similarly, three compounds <strong>(7, 11,</strong> and <strong>10)</strong> displayed excellent inhibitory activity having IC₅₀ values from 9.45 ± 0.7 to 12.61 ± 0.7 µM, better than standard. Furthermore, molecular docking study of the most active compounds <strong>(7, 10</strong> and <strong>11)</strong> recorded the highest docking score. Furthermore, by means of TD-DFT analysis a relationship between IC₅₀ values and the electronic properties of these compounds can be simulated, presenting a complex relationship where lower energy gap (Eg) values, along with suitable electronegativity (χ) and electrophilicity (ω) values, are indicative of increased biological potency. In the same manner, the physiochemical properties, drug likeness and ADMET studies of the investigated compounds gives us promising results, which might open new window for searching drug candidate in this class of compounds in near future.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 8","pages":"Pages 1600-1626"},"PeriodicalIF":2.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195859","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 and Antimicrobial Screening of New 5-Aryl-3-(4-Aryl-1,3-Thiazol-2-yl)-1,2-Oxazole Derivatives","authors":"Manish R. Bhoye ,&nbsp;Abhijit Shinde ,&nbsp;Neha Mahadik ,&nbsp;Pravin C. Mhaske","doi":"10.1080/10406638.2025.2465568","DOIUrl":"10.1080/10406638.2025.2465568","url":null,"abstract":"<div><div>A new series of 5-aryl-3-(4-aryl-1,3-thiazol-2-yl)-1,2-oxazole derivatives <strong>12–27</strong> have been efficiently synthesized from 5-aryl-1,2-oxazole-3-carbothioamides <strong>7a</strong>–<strong>d</strong> and 2-bromo-1-aryl ethanone <strong>8–11</strong>. Compounds <strong>12–27</strong> were characterized by IR and NMR spectroscopy and mass spectrometry methods. Compounds <strong>12–27</strong> were evaluated for <em>in vitro</em> antimicrobial activity against <em>P. mirabilis</em>, <em>E. coli</em>, <em>S. aureus</em>, <em>B. subtilis</em>, <em>A. niger</em> and <em>C. albicans</em> strains. Amongst the sixteen derivatives, against the <em>P. mirabilis</em>, compounds <strong>12</strong>, <strong>14</strong>, <strong>16</strong>, <strong>17</strong>, <strong>18</strong>, <strong>20</strong>, <strong>21</strong>, <strong>22</strong>, <strong>23</strong>, <strong>24</strong>, <strong>26</strong>, and <strong>27</strong> exhibited good activity. The SAR exposed that for the 3,4-dimethoxyphenyl group at the C-5 position of the 1,2-oxazole, all four derivatives <strong>20–23</strong> showed good activity against <em>P. mirabilis</em>, which indicates the 3,4-dimethoxyphenyl group is essential for activity. Against the microbial strains <em>E. coli</em>, <em>B. subtilis</em>, <em>S. aureus</em>, <em>A. niger</em> and <em>C. albicans</em>, compounds <strong>12–27</strong> were found less active. The active derivatives were evaluated for cytotoxicity against normal cell line of mouse embryonic fibroblast cells (<strong>3T3L1</strong>) at 25 and 50 µg/mL concentrations and found non-cytotoxic. These results suggested that the clubbing of the 2-position of the 1,3-thiazole with the 3-position of 1,2-oxazole is less effective for a broad spectrum of activity and needs further modifications.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 8","pages":"Pages 1498-1514"},"PeriodicalIF":2.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195862","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":"Design, Synthesis, Computational Studies, and Evaluation of Triazole Acetamide Linked with Phenyl Piperazine Derivatives as Anticancer Agents Against Breast Cancer","authors":"Mira Vaishnani ,&nbsp;Akhilesh Prajapati ,&nbsp;Sabera Bijani ,&nbsp;Sejal Shah ,&nbsp;Mehnaz Kamal ,&nbsp;Mohammed Alsaweed ,&nbsp;Vicky Jain ,&nbsp;Danish Iqbal","doi":"10.1080/10406638.2025.2463385","DOIUrl":"10.1080/10406638.2025.2463385","url":null,"abstract":"<div><div>A new series of triazole acetamide linked with phenyl piperazine derivatives <strong>8a–r</strong> were synthesized by click chemistry approach and evaluated the anti-cancer activity against breast cancer. Most of the compounds were found active against breast cancer cell line MCF-7 (8.93 ± 3.08 to 65.06 ± 0.90% inhibition at 20 µM). Compound <strong>8h</strong> was found to be the most active compound (IC₅₀ value: 18.62 ± 1.41 µM) followed by the compound <strong>8g</strong> (IC₅₀ value: 50.19 ± 2.28 µM) and the morphology of cells treated with these compounds became smaller, lost their typical shape, and ability to adhere to the culture plate. It has been also observed that compound <strong>8h</strong> exhibited a better therapeutic response than doxorubicin at ≥20 µM concentration. The study was also accessed with human normal kidney cell line HEK-293. Compounds <strong>8h</strong> and <strong>8g</strong> also showed better binding potentials toward the active site of hERα-LBD (Δ<em>G</em>: −9 and −8.6 kcal/mol, respectively) proteins than their native ligand (Δ<em>G</em>: −8.4 kcal/mol). Furthermore, molecular dynamics simulation parameters confirm the complex stability of compound <strong>8h</strong> with the protein hERα-LBD. Hence, compound <strong>8h</strong> possesses better anticancer properties among all the synthesized compounds which could be further evaluated by <em>in-vitro</em> and <em>in-vivo</em> studies.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 8","pages":"Pages 1473-1497"},"PeriodicalIF":2.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195860","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 Isatin-Schiff Base and 1,2,3-Triazole Hybrids as Anti-SARS-CoV-2 Agents: DFT, Molecular Docking, and ADMET Studies","authors":"Tamer El Malah ,&nbsp;Ahmed A. El-Rashedy ,&nbsp;Omnia Kutkat ,&nbsp;Rabeh A. El Shesheny ,&nbsp;Aymn E. Rashad ,&nbsp;Ahmed H. Shamroukh","doi":"10.1080/10406638.2025.2463382","DOIUrl":"10.1080/10406638.2025.2463382","url":null,"abstract":"<div><div>This study focuses on discovering novel antiviral compounds to address challenges posed by viral mutations and drug resistance. In this work, 3-((3,5-dimethylphenyl)imino)-1-((1-substituted-1H-1,2,3-triazol-4-yl)methyl)indolin-2-one derivatives 16–21 were synthesized via two distinct routes. The first route involved click cycloaddition reactions of Schiff base 3 with various substituted azides, while the second utilized the condensation of pre-synthesized isatin hybrids 10–15 with 3,5-dimethylaniline. The structures of these newly synthesized compounds were confirmed using advanced spectroscopic techniques and elemental analysis. Furthermore, in vitro evaluations included cytotoxicity and antiviral assays against SARS-CoV-2. Cytotoxicity was assessed using crystal violet assays to determine the cytotoxic concentration (CC50) of the compounds on Vero E6 cells. Antiviral activity was also evaluated. Among the tested compounds, compound 21 exhibited moderate antiviral activity, with a CC50 of 135.3 µM and an IC50 of 44.1 µM, resulting in a safety index (SI) of 3.1. Computational studies such as molecular docking, DFT calculations, molecular dynamics simulations, and drug-likeness assessments confirmed the stability, favorable pharmacokinetics, and drug-like properties of compound 21. These findings highlight the promise of these compounds as candidates for further optimization and development as antiviral agents.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 8","pages":"Pages 1447-1472"},"PeriodicalIF":2.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195867","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":"Investigating the Anticancer Activity of Novel 1,2,4-Oxadiazole-Linked 1,2,3-Triazole Moieties via EGFR/pI3K/mTOR Cascade Down-Regulation","authors":"Mohammed Salah Ayoup ,&nbsp;Mariam Ghanem ,&nbsp;Hamida Abdel-Hamid ,&nbsp;Ibrahim Elghamry ,&nbsp;Marwa M. Abu-Serie ,&nbsp;Aliaa A. Masoud ,&nbsp;Doaa A. Ghareeb ,&nbsp;Marwa F. Harras ,&nbsp;Magda M. F. Ismail ,&nbsp;Amr Negm","doi":"10.1080/10406638.2025.2476071","DOIUrl":"10.1080/10406638.2025.2476071","url":null,"abstract":"<div><div>Malignant transformation, apoptosis prevention, drug resistance, and metastasis are all impacted by the EGFR/PI3K/Akt/mTOR pathway. Usually, mutations in lung and colon cancer alter the expression of this pathway. This led to the creation of a new hybrid of 3,5-diaryl-1,2,4-oxadiazole/1,2,3-triazoles. These hybrids were rationalized and synthesized using click reaction via the Copper catalyzed azide-alkyes cyclo-addition (CuAAC). The antiproliferative properties of the novel library were investigated against lung (A549), colon (Caco-2) cancer cell lines and human lung fibroblast (WI38). <strong>5b, 5c, 8a, 8b,</strong> and <strong>9c</strong> showed potent antiproliferative effects (IC₅₀ 9.18–12.8 µM) against lung (A549). While <strong>8a</strong> and <strong>9a</strong> showed substantial cytotoxic effects against the colon (Caco-2) cancer cell line, with IC₅₀ of 13.0 and 12.0 µM, respectively. It is evident that, in comparison to normal cells, the selective cytotoxic of compound <strong>5c</strong> (SI 9.4), <strong>8a</strong> (SI 5.1), and <strong>9c</strong> (SI 3.7) demonstrated a small selectivity for Caco-2 cells and a significantly higher selectivity for A549 lung cancer cells. Using a CqPCR assay, the powerful cytotoxic compounds <strong>5c, 8a</strong>, and <strong>9c</strong> were selected to investigate the mechanism of action of their anticancer activities. It is noteworthy that compounds <strong>5c, 8a</strong>, and <strong>9c</strong> were able to inhibit PI3K gene expression by 4.76–8.33 folds, downregulate mTOR by 4.26–4.81 folds, and downstream gene EGFR by 4.55–5.88 times. Additionally, they raised the amount of the p53 gene (a tumor suppressor gene), which bolstered their mode of action. Interestingly, docking experiments of <strong>5c, 8a,</strong> and <strong>9c</strong> demonstrated enhanced binding with the important amino acid residues in the EGFR active site (docking energy −7.13, −7.16, and −7.67 kcal/mol, respectively) in comparison to the reference drug gefitinib (−5.84 kcal/mol), which further corroborate their mode of action. The previously mentioned results indicated that the intriguing hits <strong>5c, 8a</strong>, and <strong>9c</strong> might be investigated as promising medications.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 8","pages":"Pages 1580-1599"},"PeriodicalIF":2.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195864","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":"In-Silico Analysis of Benzo-Selenadiazole Hybrids: Reactivity and Anticancer Potential Assessed Through DFT, Molecular Dynamics, Molecular Docking, and ADMET","authors":"Mohamed Enneiymy ,&nbsp;Haydar A. Mohammad-Salim ,&nbsp;Ali Oubella ,&nbsp;Jesus Vicente de Julián-Ortiz ,&nbsp;Hans Merlin Tsahnang Fofack ,&nbsp;Saad A. Alotaibi ,&nbsp;Maraf Mbah Mbake ,&nbsp;My Youssef Ait Itto","doi":"10.1080/10406638.2025.2470274","DOIUrl":"10.1080/10406638.2025.2470274","url":null,"abstract":"<div><div>Fighting cancer is challenging, but targeting apoptosis pathways offers hope. Caspases 3 and 7 cleave substrates, leading to key features like phosphatidylserine exposure, nuclear condensation, and DNA fragmentation, driving cancer cell death. This understanding aids in developing targeted therapies to selectively eliminate cancer cells. This study explores the synthesis, characterization, and in-silico analysis of carvone-isoxazoline-selenadiazole hybrids (<strong>11a–e</strong>) as potential anticancer agents. Advanced NMR techniques, including COSY, HSQC, and HMBC, confirmed the structural integrity of the benzo[1–3]selenadiazole core. Among the derivatives, <strong>11c</strong> stood out with a low HOMO-LUMO energy gap of 3.2 eV, indicating high reactivity. MEPS analysis revealed biologically active sites at −0.85 and 1.2 eV, while biological evaluations demonstrated <strong>11c</strong>’s ability to induce apoptosis <em>via</em> caspase-3 activation with an IC50 of 2.1 μM, similar to doxorubicin. Strong docking interactions with apoptosis-related proteins further support this. Mature caspases 3 and 7 cleave a broad set of substrates, ultimately leading to apoptotic features such as phosphatidylserine exposure, nuclear condensation, and DNA fragmentation. ADMET analysis revealed favorable pharmacokinetics, with a logP of 2.5, and low toxicity risks, with an LD₅₀ value of &gt;1000 mg/kg. Structure-activity relationships highlighted selenium’s pivotal role in enhancing activity. With potent anticancer properties and a promising drug profile, 11c is a compelling candidate for further cancer therapy development.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 8","pages":"Pages 1536-1558"},"PeriodicalIF":2.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195865","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":"Tetramethylguanidine-Functionalized Novel and Recyclable Nanocatalyst for the Synthesis of Pyrazolophthalazinediones","authors":"Zahra Mirzaei ,&nbsp;Manouchehr Mamaghani ,&nbsp;Mortaza Mehrdad ,&nbsp;Fateme Tavakoli ,&nbsp;Behroz Mirza","doi":"10.1080/10406638.2025.2475012","DOIUrl":"10.1080/10406638.2025.2475012","url":null,"abstract":"<div><div>The synthesis of pyrazolophthalazinediones has so far been carried out using acid, base, and ionic liquids catalysts, which in some cases are not easily recyclable, but in this work, three-component synthesis was carried out using a recyclable nanocatalyst. Therefore, a novel protocol was devised for the synthesis of pyrazolophthalazinediones by the reaction of phthalhydrazide, aryl aldehyde and 3-(1<em>H</em>-indol-3-yl)-3-oxopropanenitrile derivatives or malononitrile in ethanol and in the presence of newly synthesized Kit-6@HAp@Si(CH₂)₃-1,1,3,3-tetramethylguanidine (Kit-6@HAp@TMG) nanocatalyst with high to excellent yields (84–95%). The structure of the catalyst was determined using various analytical techniques, including FT-IR, XRD, SEM, EDX, Mapping, TEM, and TGA. The structures of the products were confirmed by spectroscopic analyses (¹³C NMR,¹H NMR, and FT-IR) and elemental analyses. The present method offers advantages, such as simplicity, high yields, and shorter reaction time, Easy method for separating the catalyst from the synthesized product, avoiding high temperatures and using low-risk solvents, atom economy, and catalyst recyclability up to four times without significant decrease in catalytic activity, which aligns with green chemistry principles.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 8","pages":"Pages 1559-1579"},"PeriodicalIF":2.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195861","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}