The Structure and Pharmacological Functions of Coumarins and Their Derivatives

Abstract

Coumarins are of many different structures. They constitute an important class of pharmacological agents possessing a range of different physiological activities including anti-cancer, anti-oxidant, anti- inflammation, anti-HIV, anti-coagulant, anti-bacterial, analgesic and comparative immune-modulation. Recently, coumarins have attracted intense research interest. Of great interest is the possibility that this class of molecules could be a source of drugs for the therapy of several diseases. These include recent insights into inhibiting cell proliferation by interfering with mitotic spindle microtubule function, decrease Matrix Metalloproteinase (MMP) activity, block the cell cycle in the S or G2/M phases to interfere with processes of cell division, suppress O2(-) generation in leukocytes, inhibit different protein kinases, modulate the signalings, induce carcinogen-detoxifying enzymes glutathione S-transferases (GSTs) and/or NAD(P)H quinine oxidoreductase (NQO1), suppress the phosphorylation of Akt/PKB as a mechanism inhibiting inflammation, progress in structure modification to increase in anti-fungal action, to broaden against bacteria spectrum, to enhance inhibiting activities of nitric oxide synthase (NOS) and cyclooxygenase (COX), to strengthen anti-oxidant activity and to exhibite a much higher cytotoxicity against human umbilical vein endothelial cell (HUVEC). With fewer non-hemorrhagic side effects than the indanedione derivatives, they can be applied as an oral anticoagulant commonly for preventing venous thromboembolism following orthopedic surgery, recurrent myocardial infarction and the treatment of systemic embolism in atrial fibrillation, together with the significant advances in the basis of drug action. It is therefore useful to build up some correlations with the data available in order to better explore the molecular and cellular mechanism of coumarin action in the treatment of diseases. This review will focus on recent advances in molecular and cellular mechanisms of coumarin action involved with the relationship between structure and activity.

Synthesis and Cytotoxic Activity of a New Group of Heterocyclic Analogues of the Combretastatins

“…Previously we found that the plant coumarin oreoselone (14) by reaction with p-toluenesulfonyl chloride gave 2-(tosyl)oreoselone (15), which showed a high activity in Pd-catalyzed desulfonative cross-coupling reactions [19]. Herein, oreoselone (14) was converted into 2-(arylethynyl)furocoumarins 16-20 by the copper-free cross-coupling reaction with arylalkynes 21a-e in the presence of p-toluenesulfonyl chloride. After the purification by column chromatography compounds 16-20 were isolated in 44%-62% yield.…”

“…The cytotoxic activity of the synthesized series of 2-(Z)-styryldihydrofurocoumarins 2,3,6-8, 3-(Z)-styrylfurocoumarins 4,5,9-13, the parent oreoselone (14) and combretastatin A-4 (1) was determined by measuring the concentration inhibiting human tumor cell viability by 50% (CTD 50 ). The CTD 50 was determined using the conventional MTT assay, which allows to estimate the number of survived cells spectrophotometrically [27].…”

“…Activated by UV-A light furocoumarins induce many biological effects, such as photocycloadditions to DNA, immune system modulation, reactions with proteins, RNA and lipids [13][14][15]. In last decades many new potential therapeutic applications for furocoumarins are found.…”

Coumarin and Biscoumarin Inhibit <i>in Vitro</i> Obesity Model

“…These compounds have the ability to engage in non-covalent interactions (hydrophobic, π-π, and electrostatic interactions as well hydrogen bonding, metal coordination, van der waals forces etc.) with various active sites in bimolecules, and thus display a wide range of biological activities, such as anticoagulant [13], antineurodegenerative [14], antioxidant [15], anticancer [16], anti-inflammatory, anti-diabetes, antidepresive [15], antimicrobial efficacies [17], etc. 4-hydroxycoumarin derivatives of natural or synthetic origin has attracted much interest in several fields [18]- [20].…”

Synthesis and Anti-inflammatory Activity of Novel Furochromenes

“…9 Coumarins belonging to different chemical classes have been studied. 10 There are evidences of the antiretroviral activity of coumarin derivatives and their ability to inhibit HIV integrase.…”