Many natural phyto-products as perezone (Per) exhibit anti-cancer activities. Using experimental and computational studies, it was described that Poly ADP-ribose polymerase 1(PARP-1) inhibition and the induction of oxidative stress state explain the pro-apoptotic activity of Per. The aim of this study was to evaluate two phyto-products related to Per as anti-cancer agents: hydroxyperezone (OHPer) and its monoangelate (OHPer-MAng). These molecules were structurally characterized employing thermal analysis, IR spectrophotometry and X-ray diffraction techniques. The phyto-compounds evaluated in vitro in six cancer cell lines (K562, MCF-7, MDA-MB-231, HeLa, U373, A549) and non-malignant cells determinate their cytotoxicity, type of induced cell death, ability to avoid cell migration and changes at the redox status of the cell. Using, in vitro and computational studies provided the inhibition of PARP-1 and its potential binding mode. Cell proliferation assays demonstrated that OHPer-MAng treatment significantly induces apoptosis in triple negative breast cancer (TNBC) cell line (MDA-MB-231 IC₅₀=3.53 μM), being particularly less cytotoxic to Vero cells (IC₅₀=313.92 μM), human lymphocytes (IC₅₀=221.46 μM) and rat endothelial cells (IC₅₀=> 400 μM). The treatment of MDA-MB-231 cells with OHPer-MAng showed inhibition of migration by cancer cells. The induction of an oxidative stress state, similar to other quinones and PARP-1 inhibition explains the pro-apoptotic activity of OHPer-MAng. Docking studies showed that OHPer-MAng establishes great non-bonding interactions with the lateral chains of Tyr235, Hys201, Tyr246, Ser203, Asn207, and Gly233 located at the catalytic site of PARP-1, also demonstrating the anti-cancer activity of OHPer-MAng in TNBC cell line.

许多天然植物产物如perezone（Per）均具有抗癌活性。使用实验和计算研究表明，聚ADP-核糖聚合酶1（PARP-1）的抑制作用和氧化应激状态的诱导解释了Per的促凋亡活性。这项研究的目的是评估与Per有关的两种植物产物作为抗癌药：羟基过e（OHPer）及其单天使酸酯（OHPer-MAng）。这些分子通过热分析，红外分光光度法和X射线衍射技术进行结构表征。体外评估的植物化合物六种癌细胞系（K562，MCF-7，MDA-MB-231，HeLa，U373，A549）中的细胞和非恶性细胞确定其细胞毒性，诱导的细胞死亡类型，在氧化还原状态下避免细胞迁移和改变的能力的细胞。使用，体外和计算研究提供了对PARP-1的抑制及其潜在的结合模式。细胞增殖测定证明OHPer莽治疗显著诱导三阴性乳腺癌（TNBC）细胞系的凋亡（MDA-MB-231的IC ₅₀ = 3.53μM），是特别对Vero细胞较少细胞毒性（IC ₅₀ = 313.92μM），人淋巴细胞（IC ₅₀ = 221.46μM）和大鼠内皮细胞（IC ₅₀=> 400μM）。用OHPer-MAng处理MDA-MB-231细胞显示出癌细胞迁移的抑制作用。与其他醌和PARP-1抑制类似，氧化应激状态的诱导解释了OHPer-MAng的促凋亡活性。对接研究表明，OHPer-MAng与位于PARP-1催化位点的Tyr235，Hys201，Tyr246，Ser203，Asn207和Gly233的侧链建立了强大的非键相互作用，也证明了OHPer-的抗癌活性TNBC细胞系中的MAng。