苯并恶唑-丙烯腈:可持续合成方法的双重生物活性和DNA结合。

IF 3.4 4区 医学 Q2 CHEMISTRY, MEDICINAL
ChemMedChem Pub Date : 2025-09-22 DOI:10.1002/cmdc.202500429
Marina Galić, Tamara Rohtek, Leentje Persoons, Dirk Daelemans, Mihailo Banjanac, Tea Bruketa, Marijana Radić Stojković, Marijana Hranjec
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引用次数: 0

摘要

在水介质中高效合成用于制备目标化合物,以评估体外抗增殖,抗菌和抗病毒活性。生物活性受苯基或苯并恶唑环上取代基的类型和数目的影响。被3,4-二羟基50、51、3,4,5-三氢氧基52、53和4- n, n -二乙基氨基55取代的丙烯腈对癌细胞具有较强的抗增殖作用,IC50值为0.7 ~ 5.8 μM。评估其对正常细胞活力的影响。最活跃的苯并恶唑诱导DNA损伤,并分析其与ct-DNA的相互作用。紫外/可见滴定、热熔融试验和圆二色性表明,4- n, n -二乙胺55具有插层模式,3,4-二羟基50和3,4,5-三羟基衍生物52具有部分插层模式。衍生物55诱导癌细胞凋亡和细胞周期阻滞。在所测试的苯并恶唑中,2-萘基32、3-吲哚基41和42及其对羟基衍生物48对HCoV OC43具有显著的抗病毒活性(EC50为2.1 ~ 8.5 μM)。此外,3,4-二羟基溴取代丙烯腈51对金黄色葡萄球菌(MIC 8 μM)和大肠杆菌外排泵缺失突变体(MIC 4 μM)的抑菌活性最高,羟基溴取代丙烯腈49的抑菌活性也最高。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Benzoxazole-Acrylonitriles: Dual Bioactivity and DNA Binding from a Sustainable Synthetic Approach.

Efficient synthesis in aqueous media is employed to prepare targeted compounds to evaluate antiproliferative, antibacterial, and antiviral activity in vitro. The biological activity is influenced by the type and number of substituents placed at phenyl or benzoxazole ring. Acrylonitriles substituted with 3,4-dihydroxy 50, 51, 3,4,5-tryhidroxy 52, 53, and 4-N,N-diethyl-amino 55 groups demonstrate potent antiproliferative effects against cancer cell lines, with IC50 values from 0.7 to 5.8 μM. Their impact on normal cell viability is assessed. The most active benzoxazoles induce DNA damage and are analyzed for their interaction with ct-DNA. UV/Vis titrations, thermal melting assays, and circular dichroism suggest an intercalative mode for the 4-N,N-diethylamino 55 and partial intercalation for the 3,4-dihydroxy 50 and 3,4,5-tryhidroxy derivative 52. Derivative 55 induces apoptosis and cell cycle arrest in cancer cells. Among tested benzoxazoles, significant antiviral activity against HCoV OC43 is observed for the 2-naphthyl 32, 3-indolyl 41 and 42 and p-hydroxy derivative 48 (EC50 from 2.1 to 8.5 μM). Furthermore, antibacterial activity is most effective for the 3,4-dihydroxy and bromine substituted acrylonitrile 51 against S. aureus (MIC 8 μM) and the efflux pump-deleted mutant of E. coli (MIC 4 μM), which is also observed for the hydroxy and bromine substituted 49.

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来源期刊
ChemMedChem
ChemMedChem 医学-药学
CiteScore
6.70
自引率
2.90%
发文量
280
审稿时长
1 months
期刊介绍: Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.
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