盐酸美法兰的晶体结构及其与咖啡因的结合提高了其抗肿瘤作用。

IF 4.3 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
ACS Omega Pub Date : 2025-05-15 eCollection Date: 2025-05-27 DOI:10.1021/acsomega.5c01538
Juliana Pereira da Silva, Carin Cristina da Silva Batista, Maria Lúcia Schumacher, Santiago Rodriguez, Alan Talevi, Paula Haddad, Guillermo Raul Castro, Fabio Furlan Ferreira
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引用次数: 0

摘要

盐酸美法兰(MEH)是一种具有抗肿瘤活性的化疗药物,被公认为烷基化剂。在过去的几十年里,这种药物已经被用于治疗乳腺癌和卵巢癌的患者,它也被用于治疗多发性骨髓瘤。市面上有片剂和注射剂;然而口服有一定的局限性,包括全身前消除和不完全吸收。本研究采用模拟退火方法和粉末x射线衍射数据来确定其晶体结构。该结构经Rietveld细化证实,模型与实验数据具有良好的视觉一致性。鉴于MEH在水中的溶解度较低,在Mercury程序中进行的筛选(利用CSD-Materials模块)表明可能使用各种分子合成子来增强药物的功效。研磨过程(手工和机械化学)与MEH和共成体咖啡因(CAF)一起进行,形成化学计量混合物。与MEH和CAF相关的振动特性表现为低能级。研究了不同浓度的MEH-CAF对细胞活力的影响,发现与健康的MRC-5细胞(人胎儿肺成纤维细胞)相比,MEH-CAF对HeLa细胞系(宫颈肿瘤)的细胞毒性更显著。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Crystal Structure of Melphalan Hydrochloride and Its Association with Caffeine Improves Its Antineoplastic Action.

Melphalan hydrochloride (MEH) is a chemotherapy drug with antitumor activity, recognized for its classification as an alkylating agent. Over the past few decades, the drug has been administered to patients undergoing treatment for breast and ovarian cancers, and it is also intended for the treatment of multiple myeloma. It is commercially available in tablet and injection forms; however, its oral administration presents some limitations, including presystemic elimination and incomplete absorption. This study employs a simulated annealing approach and powder X-ray diffraction data to determine its crystal structure. The structure is confirmed by Rietveld refinement, which reveals good visual agreement between the generated model and experimental data. Given that MEH has low solubility in water, a screening conducted in the Mercury program (utilizing the CSD-Materials module) indicates the potential use of various molecular synthons to enhance the drug's efficacy. Grinding processes (manual and mechanochemical) are conducted with MEH and a coformer, caffeine (CAF), to form stoichiometric mixtures. The vibrational characteristics associated with MEH and CAF show low energy levels. The effects on cell viability of the MEH-CAF combination are studied at different concentrations and reveal more significant cytotoxicity against the HeLa cell line (cervical tumor) compared to healthy MRC-5 cells (human fetal lung fibroblasts).

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来源期刊
ACS Omega
ACS Omega Chemical Engineering-General Chemical Engineering
CiteScore
6.60
自引率
4.90%
发文量
3945
审稿时长
2.4 months
期刊介绍: ACS Omega is an open-access global publication for scientific articles that describe new findings in chemistry and interfacing areas of science, without any perceived evaluation of immediate impact.
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