3-Phenylcoumarins as Inhibitors of HIV-1 Replication

Abstract

We have synthesized fourteen 3-phenylcoumarin derivatives and evaluated their anti-HIV activity. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase gene as reporter. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Six compounds displayed NF-κB inhibition, four resulted Tat antagonists and three of them showed both activities. Three compounds inhibited HIV replication with IC50 values < 25 µM. The antiviral effect of the 4-hydroxycoumarin derivative 19 correlates with its specific inhibition of Tat functions, while compound 8, 3-(2-chlorophenyl)coumarin, seems to act through a mechanism unrelated to the molecular targets considered in this research.

4D-QSAR studies of coumarin derivatives as HIV-1 integrase 3′-processing inhibitors

“…Zhao's (1997) report on coumarin derivatives opened the avenue for coumarinbased HIV-1 IN inhibitors. Many coumarin derivatives were reported subsequently as HIV-1 IN inhibitors as 3 0 -processing and strand transfer inhibitors (Mao et al, 2002;Chiang et al, 2007;Tewtrakul et al, 2007;Liu et al, 2009;Kostova et al, 2006;Al-Mawsawi et al, 2006;Bailly et al, 2005;Olmedo et al, 2012;Mahajan et al, 2009;Spino et al, 1998). Hansch (Hansch and Fujita, 1964) and Wilson (Free and Wilson, 1964) established QSAR, a tool which establishes the quantitative relationship between structural, physicochemical and conformational properties with biological activity.…”

Synthesis, cholinesterase inhibition and molecular modelling studies of coumarin linked thiourea derivatives

“…Substitution on their benzopyran ring results a change in the biological activity. Activities like antibacterial [22], anti-HIV [23], anti-cancer [24], monoamaine oxidase inhibition [25] and anticoagulant [26] have been reported. Coumarins exhibit different biological and pharmacological properties like 3-benzylideneamino coumarins have inflammatory property [27], N-substituted 4-aminometyl coumarins have nervous system stimulating activity [22], 4-3-coumarinyl-3-cyclohexyl-4-thiozoline-2-one benzylidene hydrazone derivatives have anti-tubercular activity [28], N-substituted-3-carboxamido-coumarin derivatives have antibacterial and anti-inflammatory activities [29], 3-carboxamido-7-substituted coumarins displayed inhibition against human monoamine oxidase A and B [30].…”

Photophysical and photochemical properties of novel metallophthalocyanines bearing 7-oxy-3-(m-methoxyphenyl)coumarin groups

“…On the other hand, 3-phenylcoumarin derivatives are potent antioxidant, antimicrobial [3], antiviral [4], antidepressant [5], anticoagulant [6], and vasorelaxant [7] compounds, along with the ability to inhibit peroxidases, lipoxygenase [8,9] and monoamine oxidase enzyme (MAO-B) [10].…”