Departamento de Antibióticos, Rua Prof. Moraes Rego, 1235, Universidade Federal de Pernambuco, Recife, Pernambuco, 50670-901, Brazil.
Departamento de Química Fundamental, Av. Jornalista Anibal Fernandes, s/n, Universidade Federal de Pernambuco, Recife, Pernambuco, 50740-560, Brazil.
Chem Biol Interact. 2021 Jan 5;333:109316. doi: 10.1016/j.cbi.2020.109316. Epub 2020 Dec 4.
Streptomyces hygroscopicus UFPEDA 3370 was fermented in submerged cultivation and the biomass extract was partitioned, obtaining a fraction purified named EB1. After purification of EB1 fraction, nigericin free acid was obtained and identified. Nigericin presented cytotoxic activity against several cancer cell lines, being most active against HL-60 (human leukemia) and HCT-116 (human colon carcinoma) cell lines, presenting IC and (IS) values: 0.0014 μM, (30.0) and 0.0138 μM (3.0), respectively. On HCT-116, nigericin caused apoptosis and autophagy. In this study, nigericin was also screened both in vitro and in silico against a panel of cancer-related kinases. Nigericin was able to inhibit both JAK3 and GSK-3β kinases in vitro and its binding affinities were mapped through the intermolecular interactions with each target in silico.
吸水链霉菌 UFPEDA 3370 经液体深层发酵培养，提取生物量，经萃取、分离，得到一个名为 EB1 的纯化部分。对 EB1 部分进行纯化后，得到游离的壬二酸，并对其进行了鉴定。壬二酸对多种癌细胞系具有细胞毒性，对 HL-60（人白血病）和 HCT-116（人结肠癌细胞）细胞系最为活跃，IC 和（IS）值分别为：0.0014 μM（30.0）和 0.0138 μM（3.0）。壬二酸在 HCT-116 上引起细胞凋亡和自噬。在这项研究中，壬二酸还在体外和计算机筛选了一组与癌症相关的激酶。壬二酸能够在体外抑制 JAK3 和 GSK-3β激酶，并且通过与每个靶标的分子间相互作用在计算机上绘制了其结合亲和力。
