Synthesis, structure-activity relationships, and mechanism of action of anti-HIV-1 lamellarin α 20-sulfate analogues.
作者： Haruka Kamiyama , Yoshinao Kubo , Hironori Sato , Naoki Yamamoto , Tsutomu Fukuda
DOI: 10.1016/J.BMC.2011.10.030
关键词: Integrase activity 、 Chemistry 、 HIV Integrase Inhibitors 、 Viral entry 、 Mechanism of action 、 Sulfate 、 Stereochemistry 、 Structure–activity relationship 、 Anti hiv 1 、 Cell culture
摘要: Lamellarin α and six different types of lamellarin 20-sulfate analogues were synthesized their structure-activity relationships investigated using a single round HIV-1 vector infection assay. All sulfates having pentacyclic core exhibited anti-HIV-1 activity at 10 μM concentration range regardless the number position sulfate group. On other hand, non-sulfated ring-opened did not affect in similar concentrations. The utilized this study exhibit unfavorable cytotoxic effect under concentrations tested (IC(50)>100 μM). Confocal laser scanning microscopic analysis indicated that hydrophilic hardly incorporated cell. Env-mediated cell-cell fusion was suppressed by sulfates. These results suggested have novel besides previously reported integrase inhibition, possibly viral entry step replication.
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