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Enantiomeric chromene derivatives with anticancer effects from Mallotus apelta.
Bioorganic Chemistry ( IF 4.5 ) Pub Date : 2020-09-08 , DOI: 10.1016/j.bioorg.2020.104268
Phan Van Kiem 1 , Nguyen Xuan Nhiem 1 , Nguyen Hoang Anh 2 , Duong Thi Hai Yen 3 , Nguyen The Cuong 4 , Bui Huu Tai 1 , Pham Hai Yen 3 , Nguyen Hoai Nam 3 , Chau Van Minh 3 , Pham The Chinh 5 , Yu Hyun Jeon 6 , Seon Ju Park 7 , Seung Hyun Kim 6 , So Hee Kwon 6
Affiliation  

Mallotus apelta (Lour.) Müll.Arg has been used in traditional medicine for the treatment of chronic hepatitis. Six new chromene derivatives, malloapeltas C-H (16) and one known compound, malloapelta B (7) were isolated and structured from the leaves of M. apelta. Two pairs of enantiomers (1a/1b and 2a/2b) were successfully separated by chiral high-pressure liquid chromatography (HPLC). The structures and absolute configurations of compounds were determined using spectroscopic methods, including 1D, 2D NMR, and MS and quantum chemical calculation methods. All compounds were evaluated for cytotoxic activity using cell counting kit-8 (CCK-8) assay against ovarian cancer cell line (TOV-21G). Compounds 15 and 7 exhibited significant growth and viability inhibitory effects with GI50 values ranging from 0.06 to 10.39 μM and IC50 values ranging from 1.62 to 10.42 μM on ovarian cancer cell line, TOV-21G. The most cytotoxic compounds 2, 3, and 7 were chosen for studying in apoptosis mechanism. Compounds 2, 3, and 7-induced apoptosis as evidenced by activated caspase 8, caspase 9, and PARP, increased Bak and Bax, and decreased Bcl-xL and survivin. Moreover, compounds 2, 3, and 7 significantly inhibited the NF-κB signaling pathway. Taken together, our findings propose the potential application of compounds 2, 3, and 7 for treating cancer via modulating NF-κB activity.



中文翻译:

对虾色烯衍生物具有抗癌作用,来自Mallotus apelta。

Mallotus  apelta  (Lour。)Müll.Arg已在传统药物中用于治疗慢性肝炎。六个新的色烯衍生物,malloapeltas CH(1 - 6)和一个已知的化合物,malloapelta B(7)分离并从叶片结构M. 背叶。两对对映异构体(1a / 1b2a / 2b通过手性高压液相色谱法(HPLC)成功分离)。使用包括1D,2D NMR和MS在内的光谱方法和量子化学计算方法确定化合物的结构和绝对构型。使用针对卵巢癌细胞系(TOV-21G)的细胞计数试剂盒8(CCK-8)分析评估了所有化合物的细胞毒活性。化合物1 - 57表现出显著生长和生存力与GI抑制作用50个值范围从0.06到10.39μM和IC 50个值范围为1.62至10.42μM对卵巢癌细胞系,TOV-21G。最细胞毒性化合物237选择用于研究细胞凋亡的机制。化合物237个诱导的细胞凋亡所证明通过胱天蛋白酶8活化,胱天蛋白酶9,和PARP,增加Bak和Bax表达,并减少了Bcl-xL和存活。此外,化合物237显著抑制NF-κB信号传导途径。总之,我们的研究结果提出化合物的潜在应用237用于通过调节NF-κB活性而治疗癌症。

更新日期:2020-09-12
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