In vitro anti-HIV-1 activity of salicylidene acylhydrazide compounds.
In vitro anti-HIV-1 activity of salicylidene acylhydrazide compounds.
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DOI：
10.1016/j.ijantimicag.2012.05.023
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发表时间：
2012-10
影响因子：
10.8
通讯作者：
Peterson E
中科院分区：
文献类型：
--
作者：
Forthal DN;Phan TB;Slepenkin AV;Landucci G;Chu H;Elofsson M;Peterson E
Salicylidene acylhydrazide compounds have been shown to inhibit bacterial pathogens, including Chlamydia and Neisseria gonorrhoeae. If such compounds could also target HIV-1, their potential use as topical microbicides to prevent sexually transmitted infections would be considerable. We determined the in vitro anti-HIV-1 activity, cytotoxicity and mechanism of action of several salicylidene acylhydrazides. Inhibitory activity was assessed using TZMbl cells and primary peripheral blood mononuclear cells (PBMCs) as targets for HIV-1 infection. Anti-viral activity was measured against cell-free and cell-associated virus and in vaginal fluid and semen simulants. Since the anti-bacterial activity of salicylidene acylhydrazides is reversible by Fe2+, we determined whether Fe2+ and other cations could reverse the anti-HIV-1 activity of the compounds. We also employed real-time PCR to determine the stage affected in the HIV-1 replication cycle. We identified four compounds with 50% HIV-1 inhibitory concentrations of 1 to 7 μM. In vitro toxicity varied but was generally limited. Activity was similar against three R5 clade B primary isolates and whether targets for virus replication were TZMbl cells or PBMCs. Compounds inhibited cell-free and cell-associated virus and were active in vaginal fluid and semen simulants. Fe2+, but not other cations, reversed the anti-HIV-1 effect. Finally, inhibitory effect of the compounds occurred at a post-integration step. We identified salicylidene acylhydrazides with in vitro anti-HIV-1 activity in the μM range. The activity of these compounds against other sexually transmitted pathogens makes them potential candidates to formulate for use as a broad-spectrum topical genital microbicide.
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DOI：
10.1016/j.ijantimicag.2010.03.018
发表时间：
2010-08
影响因子：
10.8
作者：
Chu H;Slepenkin A;Elofsson M;Keyser P;de la Maza LM;Peterson EM
通讯作者：
Peterson EM
影响因子：
3.1
作者：
Nordfelth, R;Kauppi, AM;Elofsson, M
通讯作者：
Elofsson, M
影响因子：
3.5
作者：
Bailey, Leslie;Gylfe, Asa;Bergstrom, Sven
通讯作者：
Bergstrom, Sven
影响因子：
8.8
作者：
Traoré, HN;Meyer, D
通讯作者：
Meyer, D
影响因子：
3.5
作者：
Jin, Yinxue;Tan, Zhiwu;Yang, Ming
通讯作者：
Yang, Ming