Synthesis of Novel Heterocyclic Ferrocenyl Chalcones and Their Biological Evaluation.
Synthesis of Novel Heterocyclic Ferrocenyl Chalcones and Their Biological Evaluation.
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DOI：
10.1021/acsomega.3c01830
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发表时间：
2023-09-26
期刊：
影响因子：
4.1
通讯作者：
Montes-Gonzalez, Ingrid C.
中科院分区：
文献类型：
--
作者：
Alsina-Sanchez, Ambar M.;Montalvo-Vazquez, Sebastian;Grafals-Ruiz, Nilmary;Acosta, Carmen;Orme, Emily M.;Rodriguez, Israel;Delgado-Rivera, Sara M.;Tinoco, Arthur D.;Dharmawardhane, Suranganie;Montes-Gonzalez, Ingrid C.
乳腺癌是目前最常见的诊断癌症，据美国癌症协会报告，2022年估计有287，850例新病例。因此，找到一种有效的治疗这种疾病的方法势在必行。查耳酮是自然界中发现的α，β-不饱和体系。这些化合物显示出广泛的生物活性，使其成为受欢迎的合成目标。查耳酮由两个芳香取代基通过烯酮桥连接组成;这种排列允许大量的衍生物。考虑到这些化合物的生物相关性，基于混合药物设计方法合成并表征了新的含二茂铁杂环的查耳酮。这些杂环包括噻吩、嘧啶、噻唑基和吲哚基。合成并表征了14种新型杂环二茂铁基查耳酮。在此，我们还报告了它们对三阴性乳腺癌细胞系MDA-MB-231和4 T1以及非癌肺细胞系MRC-5的细胞毒性。系统3的二茂铁基查耳酮显示出优越的上级抗癌性能相比，他们的系统1类似物。带有五元杂环取代基（噻吩、吡唑、吡咯和嘧啶）的系统3查耳酮对MDA-MB-231癌细胞系最具活性，IC 50值为6.59 - 12.51 μM。评价化合物在4 T1细胞系中的细胞毒性显示IC 50值为13.23 - 213.7 μM。系统3吡唑查耳酮对两种细胞系具有一致的毒性（IC 50 ≤ 13 μM），并且相对于非癌MRC-5对照具有有希望的选择性。抗氧化活性也进行了评价，其中，相反的抗癌能力，系统1二茂铁基查耳酮是上级他们的系统3类似物。抗氧化活性与抗坏血酸相当的噻吩轴承二茂铁基查尔酮的EC 50 = 31 μM。
Breast cancer is currently the most commonly diagnosed cancer, with 287,850 new cases estimated for 2022 as reported by the American Cancer Society. Therefore, finding an effective treatment for this disease is imperative. Chalcones are α,β-unsaturated systems found in nature. These compounds have shown a wide array of biological activities, making them popular synthetic targets. Chalcones consist of two aromatic substituents connected by an enone bridge; this arrangement allows for a large number of derivatives. Given the biological relevance of these compounds, novel ferrocene-heterocycle-containing chalcones were synthesized and characterized based on a hybrid drug design approach. These heterocycles included thiophene, pyrimidine, thiazolyl, and indole groups. Fourteen novel heterocyclic ferrocenyl chalcones were synthesized and characterized. Herein, we also report their cytotoxicity against triple-negative breast cancer cell lines MDA-MB-231 and 4T1 and the noncancer lung cell line MRC-5. System 3 ferrocenyl chalcones displayed superior anticancer properties compared to their system 1 analogues. System 3 chalcones bearing five-membered heterocyclic substituents (thiophene, pyrazole, pyrrole, and pyrimidine) were the most active toward the MDA-MB-231 cancer cell line with IC50 values from 6.59 to 12.51 μM. Cytotoxicity of the evaluated compounds in the 4T1 cell line exhibited IC50 values from 13.23 to 213.7 μM. System 3 pyrazole chalcone had consistent toxicity toward both cell lines (IC50 ∼ 13 μM) as well as promising selectivity relative to the noncancer MRC-5 control. Antioxidant activity was also evaluated, where, contrary to anticancer capabilities, system 1 ferrocenyl chalcones were superior to their system 3 analogues. Antioxidant activity comparable to that of ascorbic acid was observed for thiophene-bearing ferrocenyl chalcone with EC50 = 31 μM.
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影响因子：
5.5
作者：
Alfieri ML;Panzella L;Amorati R;Cariola A;Valgimigli L;Napolitano A
通讯作者：
Napolitano A
影响因子：
1.1
作者：
BROWNLIE, IT;INGOLD, KU
通讯作者：
INGOLD, KU
DOI：
10.1007/s11626-015-9919-6
发表时间：
2015-10-01
影响因子：
2.1
作者：
Janka, Vaskova;Zatko, Daniel;Gabriela, Mojzisova
通讯作者：
Gabriela, Mojzisova
影响因子：
5.1
作者：
Ratkovic, Zoran;Juranic, Zorica D.;Joksovic, Milan D.
通讯作者：
Joksovic, Milan D.
影响因子：
5.6
作者：
Al-Khaldi, Alanoud;Ghoneim, Amira Atef;Zafar, Rehman
通讯作者：
Zafar, Rehman