Chemical constituents and anti-herpes simplex virus activity of Micromelum hirsutum and Glycosmis parva

Abstract

Chemical investigation of Micromelum hirsutum Oliv. and Glycosmis parva Criab led to the isolation of three coumarins, six acridone alkaloids, three limoniods, five N-[(4-monoterpenyloxy)phenylethyl]-substituted sulfur-containing propanamide derivatives and a 4-quinolone alkaloid. The structure determination of these compounds was accomplished by spectroscopic analyses (UV, IR, MS and NMR properties) and by comparison with previously reported data of known compounds. The branches of Micromelum hirsutum Oliv. provided a new natural quinolone alkaloid, namely 1,2-dimethyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid [262], two known coumarins identified as scopoletin [41] and micromelin [5] whereas the leaves afforded two known coumarins, micromelin [5] and ()-(2′S, 3′R)-3′-senecioyloxymarmesin [263]. The branches of Glycosmis parva Craib yielded a new acridone alkaloid, namely glycosparvarine (1,3,5-trihydroxy-2-methoxy-N-methyl-9-acridone) [266], together with four known acridone alkaloids (N-methylatalaphylline [258], glycofolinine [163], citramine [264] and N-methylcyclo-atalaphylline-A [265]) and three limonoids (limonin [267] and a mixture of limonexic acid [268] and isolimonexic acid [269]). From the leaves of Glycosmis parva Craib, three new N-[(4-monoterpenyloxy)phenylethyl]-substituted sulfur-containing propanamide derivatives, namely (+)-S-deoxydihydroglyparvin [270], (+)-S-deoxytetrahydroglyparvin [271] and (+)-tetrahydroglyparvin [272], two known N-[(4-monoterpenyloxy)phenylethyl]-substituted sulfur-containing propanamide derivatives (glyparvin-A [214] and (+)-dihydroglyparvin [213]) and a known acridone alkaloid, arborinine, were obtained. The isolated compounds were evaluated for their antiviral activity against HSV-1 and HSV-2. Among them, glycosparvarine [266], glycofolinine [163] and (+)-tetrahydroglyparvin [272] exhibited moderate activities against both HSV-1 and HSV-2 with EC50 of 151 µM, 348 µM and 229 µM, respectively. (+)-S-deoxydihydroglyparvin [270] exhibited activities with lower EC50 of 29.8 and 44.6 µM against HSV-1 and HSV-2, respectively