Mechchate Hamza, Costa de Oliveira Regiane, Es-Safi Imane, Vasconcelos Mourão Emmily Myrella, Bouhrim Mohamed, Kyrylchuk Andrii, Soares Pontes Gemilson, Bousta Dalila, Grafov Andriy
Laboratory of Biotechnology, Environment, Agri-Food, and Health (LBEAS), Faculty of Sciences, University Sidi Mohamed Ben Abdellah (USMBA), Fez B.P. 1796, Morocco.
Post-Graduate Program in Haematology, School of Health Sciences, University of the State of Amazonas, Av. Djalma Batista 3578, Manaus 69050-010, AM, Brazil.
Pharmaceuticals (Basel). 2021 Aug 5;14(8):770. doi: 10.3390/ph14080770.
Leukemia is a group of hematological neoplastic disorders linked to high mortality rates worldwide, but increasing resistance has led to the therapeutic failure of conventional chemotherapy. This study aimed to evaluate in vitro the antileukemic activity and potential mechanism of action of a polyphenolic extract obtained from the seeds of L. (CSP). A methylthiazoletetrazolium assay was performed to assess the CSP cytotoxicity on chronic (K562) and acute (HL60) myeloid leukemia cell lines and on normal Vero cell line. CSP toxicity was also evaluated in vivo using the OECD 423 acute toxicity model on Swiss albino mice. The results demonstrated a remarkable antitumoral activity against K562 and HL60 cell lines (IC = 16.86 µM and 11.75 µM, respectively) although no cytotoxicity was observed for the Vero cells or mice. A silico study was performed on the following receptors that are highly implicated in the development of leukemia: kinase, , , and . The molecular docking demonstrated a high affinity interaction between the principal CSP components and the receptors. Our findings demonstrated that CSP extract has remarkable antileukemic activity, which is mainly mediated by the flavonoids, catechins, and rutin, all of which showed the highest binding affinity for the targeted receptors. This study revealed a promising active compound alternative research-oriented biopharmacists to explore.
白血病是一组血液系统肿瘤性疾病，在全球范围内死亡率很高，但耐药性增加导致传统化疗治疗失败。本研究旨在体外评估从L.种子中获得的多酚提取物（CSP）的抗白血病活性及其潜在作用机制。采用甲基噻唑基四氮唑法评估CSP对慢性髓系白血病细胞系（K562）、急性髓系白血病细胞系（HL60）以及正常Vero细胞系的细胞毒性。还使用经合组织423急性毒性模型在瑞士白化小鼠体内评估CSP的毒性。结果表明，CSP对K562和HL60细胞系具有显著的抗肿瘤活性（IC50分别为16.86 μM和11.75 μM），尽管未观察到对Vero细胞或小鼠的细胞毒性。对在白血病发生中高度相关的以下受体进行了计算机模拟研究：激酶、、、和。分子对接表明CSP主要成分与这些受体之间存在高亲和力相互作用。我们的研究结果表明，CSP提取物具有显著的抗白血病活性，主要由黄酮类化合物、儿茶素和芦丁介导，所有这些成分对靶向受体均显示出最高的结合亲和力。本研究为以研究为导向的生物药剂师揭示了一种有前景的活性化合物以供探索。
