Polycyclic Aromatic Compounds最新文献_第6页

Synthesis, Bioactivities, and in Silico Studies of Novel Benzo[d][1,3]Dioxole-Based Pyrazoline Sulfonamides 新型苯并[d][1,3]二恶唑基吡唑啉磺胺类化合物的合成、生物活性及硅基研究

IF 2.6 3区化学 Q2 CHEMISTRY, ORGANIC

Polycyclic Aromatic Compounds

Pub Date : 2025-10-21 Epub Date: 2025-05-20 DOI: 10.1080/10406638.2025.2498144

Mehtap Tugrak Sakarya , Halise Inci Gul , Cem Yamali , Hiroshi Sakagami , Ruya Saglamtas , Yusuf Sert , Ilhami Gulcin

In this study, benzo[d][1, 3]dioxole-based pyrazoline sulfonamides were investigated for their biological effects on carbonic anhydrases (CAs), acetylcholinesterase (AChE), and the growth of cancer/noncancer cell lines. The synthesized 11 compounds were tested for cytotoxic efficacy against four human OSCC cell lines (Ca9-22, HSC-2, HSC-3, HSC-4) and three human normal oral cells (HGF, HPLF, and HPC). The CC₅₀ values were in the range of 9.6–28.1 µM (toward Ca9-22), 10.3–44.0 µM (HSC-2), 8.6–32.1 µM (HSC-3) and 7.7–29.5 µM (HSC-4). All of these compounds showed reduced viable cell number of all oral cancer cells dose-dependently and ultimately killed them at the higher concentration (25 ∼ 100 µM), in contrast to the reference compound 5-FU that showed cytostatic growth inhibition without killing out even at the highest concentration (1000 µM). Among the series, compounds 7 (TS = 7.0, PSE= 22.4), 10 (TS = 9.0, PSE= 49.6), and 11 (TS = 6.9, PSE= 28.4) exhibited comparable antitumor-potential with reference drug 5-FU (TS = 13.0, PSE = 17.1), based on tumor-selectivity index (TS) and potency selectivity expression (PSE) values. In addition, compounds 7, 6, and 1 showed the most potent inhibition of hCA I (Ki = 17.23 ± 4.96 µM), hCA II (Ki = 3.10 ± 0.05 µM), and AChE (Ki = 0.26 ± 0.005 nM) in bioassays. To gain deeper insight into the electronic properties of the studied molecules, frontier molecular orbital and molecular electrostatic potential analyses were performed using density functional theory. Molecular docking studies were conducted to comprehend the interactions between enzymes studied and lead compounds 1, 6, and 7. Compounds 7 and 6 formed strong hydrogen bonds with key residues of hCA I and hCA II and these interactions likely contribute to its enhanced inhibitory effect. Compound 1 also displayed strong hydrogen bonds with key residues for acetylcholinesterase inhibition. Enzyme inhibition and cytotoxicity study findings have revealed promising lead compounds, which can serve as templates for designing novel molecules in drug discovery.

本研究研究了苯并[d][1,3]二恶唑基吡唑啉磺胺类药物对碳酸酐酶（CAs）、乙酰胆碱酯酶（AChE）及肿瘤/非肿瘤细胞系生长的生物学效应。研究了合成的11种化合物对4种人OSCC细胞系（Ca9-22、HSC-2、HSC-3、HSC-4）和3种人正常口腔细胞（HGF、HPLF和HPC）的细胞毒作用。CC50值分别为9.6 ~ 28.1µM（向Ca9-22方向）、10.3 ~ 44.0µM （HSC-2方向）、8.6 ~ 32.1µM （HSC-3方向）和7.7 ~ 29.5µM （HSC-4方向）。所有这些化合物都显示出剂量依赖性地减少所有口腔癌细胞的活细胞数量，并最终在较高浓度（25 ~ 100µM）下杀死它们，而对照化合物5-FU即使在最高浓度（1000µM）下也显示出细胞抑制生长而不杀死它们。其中，化合物7 （TS = 7.0， PSE= 22.4）、10 （TS = 9.0， PSE= 49.6）和11 （TS = 6.9， PSE= 28.4）在肿瘤选择性指数（TS = 13.0， PSE= 17.1）和效价选择性表达（PSE）方面与参比药物5-FU （TS = 13.0， PSE= 17.1）具有相当的抗肿瘤潜能。此外，化合物7、6和1对hCA I （Ki = 17.23±4.96µM）、hCA II （Ki = 3.10±0.05µM）和AChE （Ki = 0.26±0.005 nM）的抑制作用最强。为了更深入地了解所研究分子的电子性质，利用密度泛函理论进行了前沿分子轨道和分子静电势分析。通过分子对接研究来了解所研究的酶与先导化合物1、6和7之间的相互作用。化合物7和6与hCA I和hCA II的关键残基形成了强氢键，这些相互作用可能有助于增强其抑制作用。化合物1与抑制乙酰胆碱酯酶的关键残基也显示出强氢键。酶抑制和细胞毒性的研究发现揭示了有前途的先导化合物，这些先导化合物可以作为药物开发中设计新分子的模板。

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引用次数: 0

Green Synthesis of Novel Naphthyridines Using Multicomponent Reactions of Isocyanates: Investigation of Biological Activity 异氰酸酯多组分绿色合成新型萘嘧啶的生物活性研究

IF 2.6 3区化学 Q2 CHEMISTRY, ORGANIC

Polycyclic Aromatic Compounds

Pub Date : 2025-10-21 Epub Date: 2025-08-01 DOI: 10.1080/10406638.2025.2524352

Nasir Iravani (Writing – original draft Writing – review & editing)

This manuscript delineates a systematic approach for the synthesis of naphthyridines utilizing arylidenemalononitrile, malononitrile, aniline, acetylenic esters, and isocyanates. The synthetic method is executed at ambient temperature without the use of solvents, incorporating a recyclable catalyst identified as SiO₂/Fe₃O₄@GO was achieved by using a water extract from the leaves of Petasits hybridus, which produces favorable outcomes. The antioxidant homes of the newly created naphthyridines are due to the presence of the NH group, which was examined using two methods called diphenyl-picrylhydrazine (DPPH) radical scavenging and the Ferric ions (Fe³⁺) reducing potential (FRAP) test. Additionally, the antimicrobial properties of the new naphthyridines were assessed using a disk diffusion test that included two different types of bacteria, one Gram-negative and one Gram-positive, showing that the growth of bacterial cells was significantly hindered by these compounds. The method used to create naphthyridines derivatives has several benefits, such as shorter reaction times, higher product yields, and the ease of separating the catalyst from the final products through a simpler process.

这篇论文描述了一个系统的方法合成萘啶利用芳基乙烯二腈，丙二腈，苯胺，乙基酯和异氰酸酯。该合成方法在室温下进行，不使用溶剂，采用可回收催化剂SiO2/Fe3O4@GO，利用Petasits hybridus叶片的水提取物获得了良好的效果。新生成的萘嘧啶的抗氧化home是由于NH基团的存在，使用两种方法进行检测，即二苯基-吡啶肼（DPPH）自由基清除和铁离子（Fe3+）还原电位（FRAP）测试。此外，采用包括两种不同类型的细菌（一种革兰氏阴性和一种革兰氏阳性）的圆盘扩散试验评估了新型萘啶的抗菌性能，表明这些化合物显著阻碍了细菌细胞的生长。用于制造萘嘧啶衍生物的方法有几个优点，例如反应时间短，产品收率高，并且通过更简单的过程易于将催化剂与最终产品分离。

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引用次数: 0

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 1,2,3-三唑结合恶唑[5,4-d]嘧啶衍生物的合理设计与合成：体外细胞毒性和硅内分子对接模拟

IF 2.6 3区化学 Q2 CHEMISTRY, ORGANIC

Polycyclic Aromatic Compounds

Pub Date : 2025-09-14 Epub Date: 2025-03-29 DOI: 10.1080/10406638.2025.2467956

Bajam Arun , Manuri Brahmayya , Reddymasu Sreenivasulu , Dasari Sravani , Suresh Dodda , Ravi Kumar Kapavarapu , Srimathi Krishnaswamy

A new series of 1,2,3-Triazole incorporated oxazolo[5,4-d]pyrimidine derivatives 24a-j were designed, synthesized and evaluated for their anticancer activity against MCF-7, A549, Colo-205, & A2780 cell lines by using MTT reduction protocol with Etoposide as positive control. Among the screened derivatives, the compound 24a 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 24h 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, 24a and 24h. The compounds 24a and 24h showed molecular interactions with human topoisomerase IIβ protein and having binding energies are −5.7 and −5.8 kcal/mole, respectively.

设计合成了一系列新的1,2,3-三唑类恶唑[5,4-d]嘧啶衍生物24a-j，并以依托泊苷为阳性对照，采用MTT还原法对MCF-7、A549、Colo-205和A2780细胞株进行了抗癌活性评价。化合物24a对MCF-7和A549细胞株的IC50值分别为0.11±0.086和0.13±0.094µM，化合物24h对MCF-7和A549细胞株的IC50值分别为0.18±0.071和0.33±0.067µM，具有较强的抗癌活性。这些活性比标准药物依托泊苷活性更有效。因此，这两种衍生物可用于癌症化疗的进一步研究。这一抗癌数据也得到了强效衍生物24a和24h的对接评分的支持。化合物24a和24h与人拓扑异构酶i β蛋白表现出分子相互作用，结合能分别为- 5.7和- 5.8 kcal/mol。

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引用次数: 0

Design, Synthesis, Antiproliferative Activity and In Silico Studies of 2-Oxo-1,2-Dihydroquinolin Derivatives 2-氧-1,2-二氢喹啉衍生物的设计、合成、抗增殖活性及硅研究

IF 2.6 3区化学 Q2 CHEMISTRY, ORGANIC

Polycyclic Aromatic Compounds

Pub Date : 2025-09-14 Epub Date: 2025-02-04 DOI: 10.1080/10406638.2025.2459212

Eman A. E. El-Helw , Eman A. Ghareeb , Naglaa F. H. Mahmoud , Eman A. El-Bordany , Elsayed A. Soliman , Khaled Abouzid , Ahmed El-Khouly

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 in vitro antiproliferative activity against MCF7 and HCT116 human cancer cell lines. Antiproliferative activity revealed that compound 11 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 4 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.

喹啉类化合物长期以来一直被认为是开发各种生物活性化合物的多功能支架。在此背景下，利用查尔酮和硫代碳腙衍生物这两个关键的构建块，设计并合成了一系列喹啉类化合物。这些化合物是根据基于双吲哚基马来酰亚胺的PDK1 atp竞争抑制剂BIM-1的设计策略合成的。最终化合物对MCF7和HCT116人癌细胞的体外抗增殖活性进行了评价。抗增殖活性表明，化合物11对HCT116和MCF7的IC50分别为7.09µM和6.18µM。此外，对PDK1酶进行了硅分子对接研究，以研究化合物在atp结合位点的结合亲和力。对接分析提供了对这些化合物的分子相互作用和结合模式的深入了解。化合物4的亲和力最高，结合分数为−11 kcal/mol， Ki值为8.65 nM。此外，ADME（吸收、分布、代谢和排泄）预测显示了良好的药物相似性和口服生物利用度。本研究旨在为开发有前景的抗癌药物做出贡献。

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引用次数: 0

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 揭示靶向MCF-7癌细胞中EGFR激酶抑制的1,2,3-三唑-异烟酸衍生物的抗癌潜力：设计、合成、生物学评价和计算机研究

IF 2.6 3区化学 Q2 CHEMISTRY, ORGANIC

Polycyclic Aromatic Compounds

Pub Date : 2025-09-14 Epub Date: 2025-04-26 DOI: 10.1080/10406638.2025.2490142

Asma Khalaf Alshamari , Faiza I. A. Abdella , Aljazi Abdullah AlRashidi , Mona Zaheed Alshammari , Hissah Khashman Alshammari , Nuha Othman S. Alsaif , Tamer El Malah

Click chemistry was used to synthesize a new library of 1,2,3-triazole-isonicotinate derivatives 8–13 using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) between mono- or bis 2,6-ethynylisonicotinate 3,4, and aromatic azides derivatives 5–7 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 13 and 10 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 13 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 13, hold potential as candidates for further investigation as anticancer agents for breast cancer treatment.

利用Click化学方法，利用铜(I)催化叠氮化物-炔环加成（CuAAC），在单-或双2,6-乙基异烟酸3,4和芳香叠氮化物衍生物5-7之间合成了1,2,3-三唑-异烟酸衍生物8-13，收率高（89-96%）。这些化合物对肝细胞癌（Hep-G2）、乳腺癌（MCF-7）和结肠癌（HCT-116）细胞系以及健康的非癌性皮肤成纤维细胞系（BJ-1）的抗增殖活性进行了评估。与参比药物相比，所有新的三唑-异烟酸化合物对结肠癌和乳腺癌细胞的细胞毒性均显著增强，而化合物13和10对肝癌细胞的细胞毒性中等。分子对接研究将化合物的生物活性与其在相关生物靶标中与蛋白质-配体复合物建立稳定相互作用的能力联系起来。化合物13在MCF-7细胞中表现出很强的诱导凋亡和细胞周期阻滞的能力，同时对表皮生长因子受体（EGFR）具有显著的抑制活性。这些初步研究结果表明，1,2,3-三唑-异烟酸酯衍生物，特别是化合物13，作为乳腺癌治疗的抗癌药物，具有进一步研究的潜力。

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引用次数: 0

Synthesis, Tyrosinase Inhibition, Molecular Docking, and DFT Studies of Amide Derivatives of Fexofenadine 非索非那定酰胺类衍生物的合成、酪氨酸酶抑制、分子对接及DFT研究

IF 2.6 3区化学 Q2 CHEMISTRY, ORGANIC

Polycyclic Aromatic Compounds

Pub Date : 2025-09-14 Epub Date: 2025-03-13 DOI: 10.1080/10406638.2025.2478141

Muhammad Ayaz , Aftab Alam , Zainab , Najeeb Ur Rehman , Ahmed A. Elhenawy , Masroor Kamal , Muhammad Arif Lodhi , Mumtaz Ali , Abdul Latif , Ahmed Al-Harrasi , Manzoor Ahmad

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 (1–12) of fexofenadine were prepared structurally deduced with the help of HR-ESIMS,¹H-, and ¹³C-NMR spectroscopy, and were screened for their in vitro tyrosinase inhibitory activity. All the synthesized products displayed excellent to moderate inhibitory activity except four compounds (1, 2, 6, and 9) which were found non-active compared with standard kojic acid (IC₅₀ = 16.9 ± 1.30 µM). Similarly, three compounds (7, 11, and 10) 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 (7, 10 and 11) 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.

酪氨酸酶是黑色素生物合成的核心酶，与皮肤疾病有关，因此抑制酪氨酸酶对化妆品和治疗应用至关重要。为寻找新的抗褐变增白剂，制备了一系列非索非那定的12个衍生物（1-12），通过HR-ESIMS、1H-和13C-NMR进行了结构推导，并对其体外酪氨酸酶抑制活性进行了筛选。除化合物1、2、6和9与标准曲酸相比无活性（IC50 = 16.9±1.30µM）外，所有合成产物均表现出优异至中等的抑制活性。同样，3个化合物（7、11和10）的IC50值为9.45±0.7 ~ 12.61±0.7µM，表现出优异的抑制活性，优于标准化合物。在分子对接研究中，活性最高的化合物（7、10和11）的对接得分最高。此外，通过TD-DFT分析，可以模拟这些化合物的IC50值与电子性质之间的关系，其中较低的能隙（Eg）值以及适当的电负性（χ）和亲电性（ω）值表明生物效价增加。同样，所研究化合物的理化性质、药物相似性和ADMET研究也给我们带来了很好的结果，这可能在不久的将来为这类化合物的候选药物的寻找打开新的窗口。

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引用次数: 0

Synthesis and Antimicrobial Screening of New 5-Aryl-3-(4-Aryl-1,3-Thiazol-2-yl)-1,2-Oxazole Derivatives 新型5-芳基-3-（4-芳基-1,3-噻唑-2-基）-1,2-恶唑衍生物的合成及抗菌筛选

IF 2.6 3区化学 Q2 CHEMISTRY, ORGANIC

Polycyclic Aromatic Compounds

Pub Date : 2025-09-14 Epub Date: 2025-02-21 DOI: 10.1080/10406638.2025.2465568

Manish R. Bhoye , Abhijit Shinde , Neha Mahadik , Pravin C. Mhaske

A new series of 5-aryl-3-(4-aryl-1,3-thiazol-2-yl)-1,2-oxazole derivatives 12–27 have been efficiently synthesized from 5-aryl-1,2-oxazole-3-carbothioamides 7a–d and 2-bromo-1-aryl ethanone 8–11. Compounds 12–27 were characterized by IR and NMR spectroscopy and mass spectrometry methods. Compounds 12–27 were evaluated for in vitro antimicrobial activity against P. mirabilis, E. coli, S. aureus, B. subtilis, A. niger and C. albicans strains. Amongst the sixteen derivatives, against the P. mirabilis, compounds 12, 14, 16, 17, 18, 20, 21, 22, 23, 24, 26, and 27 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 20–23 showed good activity against P. mirabilis, which indicates the 3,4-dimethoxyphenyl group is essential for activity. Against the microbial strains E. coli, B. subtilis, S. aureus, A. niger and C. albicans, compounds 12–27 were found less active. The active derivatives were evaluated for cytotoxicity against normal cell line of mouse embryonic fibroblast cells (3T3L1) 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.

以5-芳基-1,2-恶唑-3-碳硫酰胺7a-d和2-溴-1-芳基乙酮8-11为原料，合成了一系列新的5-芳基-3-（4-芳基-1,3-噻唑-2-基）-1,2-恶唑衍生物12-27。化合物12 ~ 27通过IR、NMR、质谱等方法进行了表征。对化合物12 ~ 27的体外抑菌活性进行了评价，测定了化合物对奇异假单胞菌、大肠杆菌、金黄色葡萄球菌、枯草芽孢杆菌、黑曲霉和白色念珠菌的抑菌活性。其中化合物12、14、16、17、18、20、21、22、23、24、26和27对mirabilis具有较好的活性。SAR结果表明，1,2-恶唑C-5位的3,4-二甲氧基对P. mirabilis的活性均较好，表明3,4-二甲氧基对活性起重要作用。化合物12 ~ 27对大肠杆菌、枯草芽孢杆菌、金黄色葡萄球菌、黑曲霉和白色念珠菌活性较低。活性衍生物在25和50µg/mL浓度下对小鼠胚胎成纤维细胞（3T3L1）的细胞毒性进行了评估，发现无细胞毒性。这些结果表明，1,3-噻唑的2位与1,2-恶唑的3位在广谱活性方面效果较差，需要进一步改进。

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引用次数: 0

Synthesis of Isatin-Schiff Base and 1,2,3-Triazole Hybrids as Anti-SARS-CoV-2 Agents: DFT, Molecular Docking, and ADMET Studies Isatin-Schiff碱和1,2,3-三唑复合物抗sars - cov -2的合成：DFT、分子对接和ADMET研究

IF 2.6 3区化学 Q2 CHEMISTRY, ORGANIC

Polycyclic Aromatic Compounds

Pub Date : 2025-09-14 Epub Date: 2025-02-13 DOI: 10.1080/10406638.2025.2463382

Tamer El Malah , Ahmed A. El-Rashedy , Omnia Kutkat , Rabeh A. El Shesheny , Aymn E. Rashad , Ahmed H. Shamroukh

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.

本研究的重点是发现新的抗病毒化合物，以解决病毒突变和耐药性带来的挑战。本文通过两种不同的途径合成了3-（（3,5-二甲基苯基）亚胺）-1-（（1-取代- 1h -1,2,3-三唑-4-基）甲基）吲哚啉-2- 1衍生物16-21。第一种途径是席夫碱3与各种取代叠氮化合物的点击环加成反应，第二种途径是利用预合成的isatin杂化物10-15与3,5-二甲苯胺的缩合反应。这些新合成的化合物的结构通过先进的光谱技术和元素分析得到了证实。此外，体外评估包括对SARS-CoV-2的细胞毒性和抗病毒试验。采用结晶紫法测定化合物对Vero E6细胞的细胞毒浓度（CC50）。抗病毒活性也进行了评估。其中化合物21具有中等抗病毒活性，CC50为135.3µM， IC50为44.1µM，安全指数（SI）为3.1。分子对接、DFT计算、分子动力学模拟和药物相似性评估等计算研究证实了化合物21的稳定性、良好的药代动力学和药物样特性。这些发现突出了这些化合物作为进一步优化和开发抗病毒药物的候选物的前景。

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引用次数: 0

Design, Synthesis, Computational Studies, and Evaluation of Triazole Acetamide Linked with Phenyl Piperazine Derivatives as Anticancer Agents Against Breast Cancer 三唑乙酰胺与苯哌嗪衍生物作为乳腺癌抗癌剂的设计、合成、计算研究和评价

IF 2.6 3区化学 Q2 CHEMISTRY, ORGANIC

Polycyclic Aromatic Compounds

Pub Date : 2025-09-14 Epub Date: 2025-02-14 DOI: 10.1080/10406638.2025.2463385

Mira Vaishnani , Akhilesh Prajapati , Sabera Bijani , Sejal Shah , Mehnaz Kamal , Mohammed Alsaweed , Vicky Jain , Danish Iqbal

A new series of triazole acetamide linked with phenyl piperazine derivatives 8a–r 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 8h was found to be the most active compound (IC₅₀ value: 18.62 ± 1.41 µM) followed by the compound 8g (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 8h 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 8h and 8g also showed better binding potentials toward the active site of hERα-LBD (ΔG: −9 and −8.6 kcal/mol, respectively) proteins than their native ligand (ΔG: −8.4 kcal/mol). Furthermore, molecular dynamics simulation parameters confirm the complex stability of compound 8h with the protein hERα-LBD. Hence, compound 8h possesses better anticancer properties among all the synthesized compounds which could be further evaluated by in-vitro and in-vivo studies.

采用点击化学方法合成了与苯基哌嗪衍生物8a-r连接的新系列三唑乙酰胺，并对其抗乳腺癌活性进行了评价。大部分化合物对乳腺癌细胞株MCF-7有抑制作用（20µM时抑制率为8.93±3.08 ~ 65.06±0.90%）。化合物8h活性最强（IC50值为18.62±1.41µM），其次是化合物8g (IC50值为50.19±2.28µM)，处理后的细胞形态变小，失去了原有的形状，不能粘附在培养板上。在浓度≥20µM时，化合物8h的治疗效果优于阿霉素。该研究还对人正常肾细胞系HEK-293进行了研究。化合物8h和8g对hERα-LBD活性位点的结合电位（分别为ΔG:−9和−8.6 kcal/mol）也优于其天然配体（ΔG:−8.4 kcal/mol）。此外，分子动力学模拟参数证实了化合物8h与hERα-LBD蛋白络合的稳定性。因此，化合物8h在所有合成的化合物中具有较好的抗癌性能，可以通过体内和体外研究进一步评价。

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引用次数: 0

Investigating the Anticancer Activity of Novel 1,2,4-Oxadiazole-Linked 1,2,3-Triazole Moieties via EGFR/pI3K/mTOR Cascade Down-Regulation 通过EGFR/pI3K/mTOR级联下调新型1,2,4-恶二唑- 1,2,3-三唑基团的抗癌活性研究

IF 2.6 3区化学 Q2 CHEMISTRY, ORGANIC

Polycyclic Aromatic Compounds

Pub Date : 2025-09-14 Epub Date: 2025-02-12 DOI: 10.1080/10406638.2025.2476071

Mohammed Salah Ayoup , Mariam Ghanem , Hamida Abdel-Hamid , Ibrahim Elghamry , Marwa M. Abu-Serie , Aliaa A. Masoud , Doaa A. Ghareeb , Marwa F. Harras , Magda M. F. Ismail , Amr Negm

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). 5b, 5c, 8a, 8b, and 9c showed potent antiproliferative effects (IC₅₀ 9.18–12.8 µM) against lung (A549). While 8a and 9a 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 5c (SI 9.4), 8a (SI 5.1), and 9c (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 5c, 8a, and 9c were selected to investigate the mechanism of action of their anticancer activities. It is noteworthy that compounds 5c, 8a, and 9c 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 5c, 8a, and 9c 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 5c, 8a, and 9c might be investigated as promising medications.

EGFR/PI3K/Akt/mTOR通路均影响恶性转化、细胞凋亡预防、耐药和转移。通常，肺癌和结肠癌的突变会改变这一途径的表达。这导致了一种新的3,5-二烷基-1,2,4-恶二唑/1,2,3-三唑的杂交产物的产生。通过铜催化叠氮烷环加成反应（CuAAC），对这些杂化物进行理顺合成。研究了该文库对肺癌（A549）、结肠癌（Caco-2）细胞系和人肺成纤维细胞（WI38）的抗增殖性能。5b、5c、8a、8b和9c对肺（A549）有较强的抗增殖作用（IC50为9.18 ~ 12.8µM）。而8a和9a对结肠（Caco-2）癌细胞表现出明显的细胞毒作用，IC50分别为13.0和12.0µM。很明显，与正常细胞相比，化合物5c （SI 9.4）、8a （SI 5.1）和9c （SI 3.7）的选择性细胞毒性对cco -2细胞的选择性较低，而对A549肺癌细胞的选择性明显较高。采用CqPCR方法，选择强效细胞毒化合物5c、8a和9c，研究其抗癌作用机制。值得注意的是，化合物5c、8a和9c能够抑制PI3K基因表达4.76 ~ 8.33倍，下调mTOR 4.26 ~ 4.81倍，下调下游基因EGFR 4.55 ~ 5.88倍。此外，他们提高了p53基因（一种肿瘤抑制基因）的数量，这加强了他们的作用模式。有趣的是，对接实验表明，与参比药物吉非替尼（- 5.84 kcal/mol）相比，5c、8a和9c与EGFR活性位点重要氨基酸残基的结合能力增强（对接能量分别为- 7.13、- 7.16和- 7.67 kcal/mol），进一步证实了它们的作用方式。前面提到的结果表明，有趣的撞击点5c， 8a和9c可能作为有前途的药物进行研究。

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引用次数: 0