Discovery of acylphloroglucinol-based meroterpenoid enantiomers as KSHV inhibitors from Hypericum japonicum.
Discovery of acylphloroglucinol-based meroterpenoid enantiomers as KSHV inhibitors from Hypericum japonicum.
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从金丝桃中发现基于酰基间苯三酚的类萜对映体作为 KSHV 抑制剂
DOI：
10.1039/c8ra04073g
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发表时间：
2018-07-02
期刊：
影响因子：
3.9
通讯作者：
Zhang, Yonghui
中科院分区：
文献类型：
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作者：
Hu, Linzhen;Liu, Yanfei;Wang, Yanxing;Wang, Zhenzhen;Huang, Jinfeng;Xue, Yongbo;Liu, Junjun;Liu, Zhenming;Chen, Yong;Zhang, Yonghui
卡波西肉瘤相关疱疹病毒（KSHV）作为一种致癌病原体已获得相当大的关注。最近的研究表明，KSHV参与了卡波西肉瘤相关的恶性肿瘤疾病的发病机制。病毒裂解性感染可能是KSHV诱导疾病的发病机制的关键;然而，大多数临床KSHV裂解性复制抑制剂如更昔洛韦、奈非那韦或西多福韦不能有效地抑制病毒复制以达到临床疗效。在我们对中草药的持续药物研究中，从田基黄中发现了新的酰基间苯三酚类对映体。这些代谢物中的大多数具有靶向KSHV裂解复制的潜在抑制活性。在这些类似物中，化合物1a和1B具有未报道的环系统环戊二烯并[B]色烯。化合物1a和4a对KSHV在Vero细胞中的裂解复制具有较强的抑制活性。此外，1a和4a的IC 50值分别为8.30和4.90 μM，选择性指数分别为23.49和25.70。定性和定量的SAR和分子对接研究酰基间苯三酚为基础的meroterpenoids抗KSHV活性进行。的活性和选择性指数的变化的解释提出了根据预测的结合位姿发现与一个假定的目标，胸苷酸合成酶（KTS）的分子对接。化合物1a和4a具有进一步开发和优化其抗KSHV活性的潜力，这可能导致新的候选药物。从田基黄中发现了新的对映体（1a/1b-4a/4 b）。1a/1 B具有环戊二烯并[B]色烯的新环系。1a和4a具有良好的抗KSHV活性。进行了对映体抗KSHV活性的QSAR研究。
Kaposi's sarcoma associated herpesvirus (KSHV) has gained considerable attention as a type of carcinogenic pathogen. Recent research suggests that KSHV has participated in the pathogenesis of Kaposi's sarcoma-related malignant neoplastic diseases. Viral lytic infection might be pivotal for the etiopathogenesis of KSHV-induced diseases; however, most clinical KSHV lytic replication inhibitors like ganciclovir, nelfinavir, or cidofovir do not restrain virus replication effectively enough to achieve clinical efficacy. In our continued pharmaceutical studies on Chinese herbal medicines, new acylphloroglucinol-based meroterpenoid enantiomers have been discovered from Hypericum japonicum. Most of these metabolites have potential inhibitory activities that target KSHV lytic replication. Amongst these analogues, compounds 1a and 1b possess an unreported ring system cyclopenta[b]chromene. Compounds 1a with 4a exhibit stronger inhibitory activities towards the lytic replication of KSHV in Vero cells. In addition, 1a and 4a have IC50 values of 8.30 and 4.90 μM and selectivity indexes of 23.49 and 25.70, respectively. Qualitative and quantitative SAR and molecular docking studies for acylphloroglucinol-based meroterpenoids with regard to anti-KSHV activity were conducted. An explanation for the variation in the activity and selectivity indexes was proposed in accordance with the predicted binding pose found with molecular docking to a putative target, thymidylate synthase (kTS). Compounds 1a and 4a have potential for further development and optimization of their anti-KSHV activities which could lead to new candidate drugs. New enantiomers (1a/1b–4a/4b) were discovered from Hypericum japonicum. 1a/1b possessed a novel ring system cyclopenta[b]chromene. 1a and 4a exhibited promising anti-KSHV activities. QSAR studies for enantiomers on anti-KSHV activity were conducted.
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影响因子：
--
作者：
Patton JT;Lustberg ME;Lozanski G;Garman SL;Towns WH;Drohan CM;Lehman A;Zhang X;Bolon B;Pan L;Kinghorn AD;Grever MR;Lucas DM;Baiocchi RA
通讯作者：
Baiocchi RA
影响因子：
12.8
作者：
Tse, Eric;Kwong, Yok-Lam
通讯作者：
Kwong, Yok-Lam
DOI：
10.3390/molecules190810733
发表时间：
2014-07-24
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Liu LS;Liu MH;He JY
通讯作者：
He JY
影响因子：
7.6
作者：
Cho, Hye-Jeong;Jeong, Seon-Gyeong;Song, Moon Jung
通讯作者：
Song, Moon Jung
影响因子：
3.8
作者：
Rosselli S;Bruno M;Maggio A;Raccuglia RA;Safder M;Lai CY;Bastow KF;Lee KH
通讯作者：
Lee KH