Design, synthesis, and antiviral activity of a series of CD4-mimetic small-molecule HIV-1 entry inhibitors.
Design, synthesis, and antiviral activity of a series of CD4-mimetic small-molecule HIV-1 entry inhibitors.
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一系列CD4模拟的小分子HIV-1进入抑制剂的设计，合成和抗病毒活性。
DOI：
10.1016/j.bmc.2021.116000
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发表时间：
2021-02-15
影响因子：
3.5
通讯作者：
Debnath AK
中科院分区：
文献类型：
--
作者：
Curreli F;Ahmed S;Benedict Victor SM;Iusupov IR;Spiridonov EA;Belov DS;Altieri A;Kurkin AV;Debnath AK
我们展示了我们在优化针对HIV-1 gp120的Phe43空洞的第二代NBD进入拮抗剂方面的持续进展。我们合成了38个NbD-14136的新的和新的类似物，这些类似物以前是基于CH2OH的“位置开关”假说设计的，并得到了一个全面的合成孔径雷达。抗病毒数据证实，直线醇朝向噻唑环的“N”(C4)比朝向噻唑环的“S”(C5)的直线醇产生了更多的活性抑制剂。最好的抑制剂NbD-14273(化合物13)对HIV-1HXB2的抗病毒活性和选择性指数(SI)均高于NbD-14136。我们还测试了NBD-14273对代表不同亚型临床分离株的50种HIV-1环境假型病毒的作用。总体平均数据表明，与NBD-14136相比，抗病毒效力提高了~3倍，SI也提高了~3倍。这一新的新型抑制剂有望为进一步优化合成更有效、更具临床意义的抗HIV-1抑制剂铺平道路。
We presented our continuing stride to optimize the second-generation NBD entry antagonist targeted to the Phe43 cavity of HIV-1 gp120. We have synthesized thirty-eight new and novel analogs of NBD-14136, earlier designed based on a CH2OH “positional switch” hypothesis, and derived a comprehensive SAR. The antiviral data confirmed that the linear alcohol towards the “N” (C4) of the thiazole ring yielded more active inhibitors than those towards the “S” (C5) of the thiazole ring. The best inhibitor, NBD-14273 (compound 13), showed both improved antiviral activity and selectivity index (SI) against HIV-1HXB2 compared to NBD-14136. We also tested NBD-14273 against a large panel of 50 HIV-1 Env-pseudotyped viruses representing clinical isolates of diverse subtypes. The overall mean data indicate that antiviral potency against these isolates improved by ~3-fold, and SI also improved ~3-fold compared to NBD-14136. This new and novel inhibitor is expected to pave the way for further optimization to a more potent and clinically relevant inhibitor against HIV-1.
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影响因子：
7.3
作者：
Curreli F;Kwon YD;Zhang H;Scacalossi D;Belov DS;Tikhonov AA;Andreev IA;Altieri A;Kurkin AV;Kwong PD;Debnath AK
通讯作者：
Debnath AK
影响因子：
7.3
作者：
Curreli, Francesca;Kwon, Young Do;Debnath, Asim K.
通讯作者：
Debnath, Asim K.
影响因子：
5.4
作者：
Blish, Catherine A.;Jalalian-Lechak, Zahra;Overbaugh, Julie
通讯作者：
Overbaugh, Julie
DOI：
10.3390/v4020309
发表时间：
2012-02
期刊：
Viruses
影响因子：
--
作者：
Didigu CA;Doms RW
通讯作者：
Doms RW
影响因子：
5.4
作者：
ADACHI, A;GENDELMAN, HE;MARTIN, MA
通讯作者：
MARTIN, MA