Phosphodiesterase Inhibitory Coumarinolignoids from Duranta repens

Abstract

Durantins A-C (1-3), new coumarinolignoids together with three known compounds cleomiscosins A (4), 6,7,8-trimethoxycoumarin (5) and 5,4′dihydroxy-3,6,7-trimethoxyflavone (6) have been isolated from a CHCl 3 soluble fraction of Duranta repens.Their structures were assigned on the basis of spectral studies.Compounds (1, 3 and 4) showed inhibitory activity against phosphodiesterase enzyme.Duranta repens is widely distributed in northern parts of Pakistan and finds various medicinal uses in the indigenous system of medicine.The fruits of this plant afford a medicine for the treatment of malaria. 1 The methanolic extract also shows insecticidal and antifeedant properties. 2 A steroid, 3 diterpenoids and C-alkylated flavonoids have previously been reported from this species. 4The ethanolic extract of this plant showed strong cytotoxicity in brine shrimp lethality test. 5Further pharmacological screening of the ethanolic extract revealed inhibitory activity against phosphodiesterase enzyme. 6The enzyme nucleotide pyrophosphatases/phosphodiesterases (NPP1) or plasma cell antigen 1 (PC-1) successively hydrolyses 5′-mononucleotides from nucleotides and their derivatives. 7They exist both as membrane proteins with an extracellular active site and as soluble proteins in body fluid. 8They are widely distributed in mammalian intestinal mucosa, mammalian liver cells, blood serum, snake venom and various plants. 6NPPs are believed to be involved in a wide variety of processes, such as bone formation, insulin resistance and metastasis of cancer cells.Inhibitors of PC-1 might be useful as treatment for some forms of arthritis. 6,9,102][13] The compounds (1, 3 and 4) showed inhibitory activity against phosphodisterase.Durantin A (1) was isolated as a creamish yellow amorphous powder.The molecular formula was determined as C 22 H 20 O 9 by an [M+H] + peak at m/z 429.1190 in HR-FAB-MS spectrometry (calcd for