TY - JOUR
T1 - Antioxidant function of phenethyl-5-bromo-pyridyl thiourea compounds with potent anti-HIV activity
AU - Dong, Yanhong
AU - Venkatachalam, T. K.
AU - Narla, Rama Krishna
AU - Trieu, Vuong N.
AU - Sudbeck, Elise A.
AU - Uckun, Fatih M.
PY - 2000/1/3
Y1 - 2000/1/3
N2 - In a systematic search for novel dual function antioxidants with potent anti-HIV activity, we evaluated 9 rationally designed non-nucleoside inhibitors (NNI) of HIV-1 RT for antioxidant and anti-HIV activities. Our lead phenethyl-5-bromopyridyl thiourea (PEPT) compounds, N-[2-(2- methoxyphenylethyl)]-N′-[2-(5-bromopyridyl)]-thiourea (2) and N-[2-(2- chlorophenylethyl)]-N′-[2-(5-bromopyridyl)]-thiourea (9), inhibited the oxidation of ABTS to ABTS+ by metmyoglobin in the presence of hydrogen peroxide with EC50 values of 79 and 75 μM, respectively. Both compounds effectively inhibited the oxidation-induced green fluorescence emission from the free radical-sensitive indicator dye 2′,7′-dichlorodihydrofluorescein diacetate in CEM human T-cells and Nalm-6 human B-cells exposed to hydrogen peroxide. To our knowledge, compounds 2 and 9 are the first NNI of HIV-1 RT with potent anti-oxidant activity. Furthermore, the activity center was defined as the sulfhydryl group since alkylated PEPT derivatives were inactive. The presence of a free thiourea group was also essential for the anti-HIV activity of the PEPT compounds.
AB - In a systematic search for novel dual function antioxidants with potent anti-HIV activity, we evaluated 9 rationally designed non-nucleoside inhibitors (NNI) of HIV-1 RT for antioxidant and anti-HIV activities. Our lead phenethyl-5-bromopyridyl thiourea (PEPT) compounds, N-[2-(2- methoxyphenylethyl)]-N′-[2-(5-bromopyridyl)]-thiourea (2) and N-[2-(2- chlorophenylethyl)]-N′-[2-(5-bromopyridyl)]-thiourea (9), inhibited the oxidation of ABTS to ABTS+ by metmyoglobin in the presence of hydrogen peroxide with EC50 values of 79 and 75 μM, respectively. Both compounds effectively inhibited the oxidation-induced green fluorescence emission from the free radical-sensitive indicator dye 2′,7′-dichlorodihydrofluorescein diacetate in CEM human T-cells and Nalm-6 human B-cells exposed to hydrogen peroxide. To our knowledge, compounds 2 and 9 are the first NNI of HIV-1 RT with potent anti-oxidant activity. Furthermore, the activity center was defined as the sulfhydryl group since alkylated PEPT derivatives were inactive. The presence of a free thiourea group was also essential for the anti-HIV activity of the PEPT compounds.
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U2 - 10.1016/S0960-894X(99)00581-8
DO - 10.1016/S0960-894X(99)00581-8
M3 - Article
C2 - 10636251
AN - SCOPUS:0034598350
SN - 0960-894X
VL - 10
SP - 87
EP - 90
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 1
ER -