6-Substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives in a new approach of the treatment of cancer cell invasion and metastasis

Abstract

Novel 6-substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives were synthesized and their potency in reducing the invasive behaviour of HT 1080 fibrosarcoma cells was evaluated. Structure-activity relationships were deduced from biological results and will be used in further design of new active compounds. In particular, the acetoxymethyl substituent found at the 6-position of previously described active compounds can be replaced by an acetamidomethyl substituent without loss of potency; while the presence of an aryl ester function at the 3-position was preferred to a thioester or an amide function to induce marked biological activity.This work confirms the interest of aryl esters of 6-substituted coumarin-3-carboxylic acids as potential new anticancer agents.

Syntheses of Coumarins in Environmentally Friendly Ionics Liquids

“…This fact suggests that neutral or basic media are not at all favorable for the coumarin synthesis. The fact is also confirmed by an experiment that the yield of the same coumarin (8) in ethanol in the presence of piperidine is quite moderate (30%-40%, measured by GC/MS in our laboratory).…”

“…After drying, the product was purified by crystallization or chromatography (silica gel; petroleum ether-EtOAc, 3:2). The reaction leads to the formation of 3-substituted coumarin derivative-2-imino-2H-1-benzopyran-3-carboxylic acid ethyl ester (8), the yield reaching 96% (Fig. 5).…”

“…The reaction does not need heating but proceed at room temperature (Scheme 2). The condensation reaction product (8) was separated from the reaction mixture by dissolving ionic liquid in water. After drying, the product was purified by crystallization or chromatography (silica gel; petroleum ether-EtOAc, 3:2).…”

“…They are also widely used in biological and medicinal research, and especially coumarin-3-carboxylic acid and other 3-substituted coumarins. These compounds have shown anticancer activity [7,8], antimicrobial activity [9], lipid lowering effect [10], a possibility to inhibite acetylcholinesterase [11], monoamine oxidase [12] and other enzymes.…”

New biological investigations on 3‐bromophenyl 6‐acetoxymethyl‐2‐oxo‐2H‐1‐benzopyran‐3‐carboxylate as anti‐angiogenic agent

“…3-Bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate (IK9) was found to be potent in inhibiting cancer cell invasion in vitro and tumor growth in vivo, with rates comparable to those observed with inhibitors of matrix metalloproteinases (MMPs) such as GI 129471, Ro 28-2653 [Kempen et al, 2003[Kempen et al, , 2008, or BB94 [Maquoi et al, 2004]. The mechanism of action of IK9 remains unknown and could not be ascribed to the inhibition of MMPs (MMP-2 and MMP-9) or serine proteases (urokinase, a-chymotrypsin, human leukocyte elastase) [Kempen et al, 2003].…”