Chaves Otávio Augusto, Cesarin-Sobrinho Dari, Serpa Carlos, da Silva Márcia Barbosa, de Lima Marco Edilson Freire, Netto-Ferreira José Carlos
Department of Chemistry, Coimbra Chemistry Centre-Institute of Molecular Sciences (CQC-IMS), University of Coimbra (UC), Rua Larga, 3004-535 Coimbra, Portugal.
Departament of Organic Chemistry, Institute of Chemistry, Federal Rural University of Rio de Janeiro (UFRRJ), Seropédica 23890-000, RJ, Brazil.
Int J Biol Macromol. 2024 Dec;283(Pt 4):137981. doi: 10.1016/j.ijbiomac.2024.137981. Epub 2024 Nov 23.
The natural products 7-hydroxycoumarin (7HC) and 7-hydroxy-4-methylcoumarin (7H4MC), known as umbelliferone and hymecromone, respectively, are one of the simplest structural examples from coumarin's family, showing several biological activities. Bovine serum albumin (BSA) is the main model protein used in laboratory experiments to characterize the biophysical capacity of potential drugs to be carried until the target in the bloodstream. Thus, the interaction BSA:7HC and BSA:7H4MC was biophysically characterized by circular dichroism (CD), steady-state, and time-resolved fluorescence techniques combined with molecular docking calculations via cross-docking approach to better correlate with the biological medium. There is a ground-state association BSA:7HC/7H4MC, and the presence of the methyl group in the coumarin core did not change the binding affinity and trend to BSA significantly. However, comparing the obtained data with those reported to benzo-α-pyrone there is evidence that the incorporation of the hydroxyl group in the aromatic ring A of the coumarin core improves the binding affinity to albumin around 10-folds and changes the binding site from subdomain IIA to IIIA or IB. In addition, the presence of other drugs, e.g., naproxen or ketoprofen, might interfere with the binding capacity of 7HC and 7H4MC, resulting in perturbations on the residence time of some clinically used drugs in the bloodstream.
天然产物7-羟基香豆素（7HC）和7-羟基-4-甲基香豆素（7H4MC），分别被称为伞形花内酯和羟甲香豆素，是香豆素家族中结构最简单的例子之一，具有多种生物活性。牛血清白蛋白（BSA）是实验室实验中用于表征潜在药物在血液中输送至靶点的生物物理能力的主要模型蛋白。因此，通过圆二色性（CD）、稳态和时间分辨荧光技术结合分子对接计算，采用交叉对接方法对BSA:7HC和BSA:7H4MC之间的相互作用进行了生物物理表征，以便更好地与生物介质相关联。存在基态结合物BSA:7HC/7H4MC，香豆素核心中甲基的存在并未显著改变其与BSA的结合亲和力和趋势。然而，将获得的数据与报道的苯并-α-吡喃的数据进行比较，有证据表明香豆素核心的芳环A中引入羟基可使与白蛋白的结合亲和力提高约10倍，并将结合位点从亚结构域IIA改变为IIIA或IB。此外，其他药物如萘普生或酮洛芬的存在可能会干扰7HC和7H4MC的结合能力，导致一些临床使用药物在血液中的停留时间受到干扰。
