Alsina-Sánchez Ámbar M, Montalvo-Vázquez Sebastián, Grafals-Ruiz Nilmary, Acosta Carmen, Ormé Emily M, Rodríguez Israel, Delgado-Rivera Sara M, Tinoco Arthur D, Dharmawardhane Suranganie, Montes-González Ingrid C
Department of Chemistry, University of Puerto Rico, Río Piedras Campus, San Juan 00931, Puerto Rico.
Department of Biochemistry, University of Puerto Rico, Medical Science Campus, San Juan 00921, Puerto Rico.
ACS Omega. 2023 Sep 11;8(38):34377-34387. doi: 10.1021/acsomega.3c01830. eCollection 2023 Sep 26.
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 IC values from 6.59 to 12.51 μM. Cytotoxicity of the evaluated compounds in the 4T1 cell line exhibited IC values from 13.23 to 213.7 μM. System 3 pyrazole chalcone had consistent toxicity toward both cell lines (IC ∼ 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 EC = 31 μM.
乳腺癌是目前最常被诊断出的癌症，据美国癌症协会报告，2022年估计有287,850例新发病例。因此，找到针对这种疾病的有效治疗方法势在必行。查耳酮是自然界中发现的α,β-不饱和体系。这些化合物已显示出广泛的生物活性，使其成为热门的合成目标。查耳酮由通过烯酮桥连接的两个芳族取代基组成；这种结构允许产生大量衍生物。鉴于这些化合物的生物学相关性，基于混合药物设计方法合成并表征了新型含二茂铁-杂环的查耳酮。这些杂环包括噻吩、嘧啶、噻唑基和吲哚基团。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4T1以及非癌性肺细胞系MRC-5的细胞毒性。与系统1类似物相比，系统3二茂铁基查耳酮表现出优异的抗癌特性。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值为6.59至12.51μM。评估的化合物在4T1细胞系中的细胞毒性表现出IC值为13.23至213.7μM。系统3吡唑查耳酮对两种细胞系均具有一致的毒性（IC ∼ 13 μM），并且相对于非癌性MRC-5对照具有良好的选择性。还评估了抗氧化活性，与抗癌能力相反，系统1二茂铁基查耳酮优于其系统3类似物。观察到含噻吩的二茂铁基查耳酮的抗氧化活性与抗坏血酸相当，EC = 31 μM。
