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Design, synthesis and evaluation of small molecule CD4-mimics as entry inhibitors possessing broad spectrum anti-HIV-1 activityстатья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 30 декабря 2016 г.
- Авторы: Curreli F., Belov D.S., Ranjith R.R., Patel N., Altieri A., Kurkin A.V., Debnath A.K.
- Журнал: Bioorganic and Medicinal Chemistry
- Том: 24
- Номер: 22
- Год издания: 2016
- Издательство: Pergamon Press Ltd.
- Местоположение издательства: United Kingdom
- Первая страница: 5988
- Последняя страница: 6003
- DOI: 10.1016/j.bmc.2016.09.057
- Аннотация: Since our first discovery of a CD4-mimic, NBD-556, which targets the Phe43 cavity of HIV-1 gp120, we and other groups made considerable progress in designing new CD4-mimics with viral entry-antagonist property. In our continued effort to make further progress we have synthesized twenty five new analogs based on our earlier reported viral entry antagonist, NBD-11021. These compounds were tested first in HIV-1 Env-pseudovirus based single-cycle infection assay as well as in a multi-cycle infection assay. Four of these new compounds showed much improved antiviral potency as well as cytotoxicity. We selected two of the best compounds 45A (NBD-14009) and 46A (NBD-14010) to test against a panel of 51 Env-pseudotyped HIV-1 representing diverse subtypes of clinical isolates. These compounds showed noticeable breadth of antiviral potency with IC50 of as low as 150 nM. These compounds also inhibited cell-to-cell fusion and cell-to-cell HIV-1 transmission. The study is expected to pave the way of designing more potent and selective HIV-1 entry inhibitors targeted to the Phe43 cavity of HIV-1 gp120.
- Добавил в систему: Белов Дмитрий Сергеевич