Synthesis, Molecular Modeling, and Selective Inhibitory Activity against Human Monoamine Oxidases of 3-Carboxamido-7-Substituted Coumarins

Abstract

A large series of 3-carboxamido-7-substituted coumarins have been synthesized and tested in vitro for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory activity. Taking into account all the relevant structural information on MAOs reported in the literature, we made some changes in the coumarin nucleus and examined with particular attention the effect on activity and selectivity of substituting at position 3 with N-aryl or N-alkyl carboxamide and at position 7 with a benzyloxy or a 4'-F-benzyloxy group. Some of the assayed compounds proved to be potent, selective inhibitors of hMAO-B with IC(50) values in the micromolar range. To better understand the enzyme-inhibitor interaction and to explain the selectivity of the most active compounds toward hMAOs, molecular modeling studies were carried out on new, high resolution, hMAO-A and hMAO-B crystallographic structures.

Efficient One-Pot Synthesis of 1,4-Dihydropyridino[3,2-c]coumarins

“…香豆素衍生物是一类广泛存在于自然界中的重要 的杂环化合物, 具有明显的抗凝结、抗癌症及抗 HIV 等 生物活性 [4] . 其中吡啶并香豆素类化合物由于具有抑制 单胺氧化酶 [5] 、抗肿瘤 [6] 、止痛 [7] 、抗菌 [8] [9] (结构式 A), 二 氢喹啉并[3,2-c]香豆素 [10] (结构式 B), 具有抗肿瘤活性 的四氢喹啉并[3,2-c]香豆素 [11] (结构式 C)等, 成为香豆 素类化合物研究领域中的一个热点. 最近, 我们以稠杂环化合物为研究对象, 先后合成 了具有潜在生物活性的含吡啶 [12] 、吡喃 [13] 、呋喃 [14] 、香 豆素 [15] [17] 受到关注, 但在碘作用下的该类反应报道不 多 [18] .…”

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

“…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]. These all suggest that selectivity towards specific target is affected by substitution of the pharmacophore.…”

Novel structurally similar chromene derivatives with opposing effects on p53 and apoptosis mechanisms in colorectal HCT116 cancer cells

“…1), another example of a natural chromene derivative, is known for its therapeutic properties for many diseases including cancer (Singh et al, 2011). Naturally occurring chromenes are now used as valuable leads for the design and synthesis of new active analogs and synthetic derivatives incorporating the chromene scaffold, where they are reported, for example, as anti-HIV agents, monoamine oxidase and interleukin-5 inhibitors, anti-inflammatory and antibacterial agents, as well as as anticancer drugs (Vasselin et al, 2006;Chimenti et al, 2009;Nam et al, 2010;Zhou et al, 2010;Gaspar et al, 2011;Kostova et al, 2011).…”