Glycosmis parva CRAIB (Rutaceae) is a wild small shrub distributed in Thailand.1) Some plants in the genus Glycosmis have been used as Thai traditional medicines for treatments of abscess, scabies, and snakebite. The genus Glycosmis is a rich source of acridone alkaloids and sulfur-containing propanamides especially in branches and leaves, respectively.
2)Biological activities of acridone alkaloids were reported such as antimalarial activity, 3) anti-herpes simplex virus (HSV) activity, 4) tumor cell growth inhibition, 5) suppression of human immunodeficiency virus type 1 (HIV-1) replication, 6) induction of human promyelocytic leukemia (HL-60) cellular differentiation, 7) antiproliferative activity, 8) cancer chemopreventive activity, 9) and modulation of P-glycoprotein activity.10) For sulfur-containing propanamides, antifungal activities were mainly reported. 11) We examined the crude extracts of the branches and leaves of G. parva focused on anti-HSV activities against HSV-1 and HSV-2 and observed positive activities. In this paper, we report the structure elucidation of a new acridone alkaloid, glycosparvarine (1), two new N- [(4-monoterpenyloxy)phenylethyl]-substituted sulfur-containing propanamide derivatives, S-deoxydihydroglyparvin (10) and S-deoxytetrahydroglyparvin (11), which were isolated together with nine known compounds, and the anti-HSV activity of the isolates.
Results and DiscussionThe MeOH extracts of the branches and the leaves of G. parva were partitioned with hexane. The remaining layers were further partitioned with EtOAc and n-BuOH after addition of water. Organic extracts were subjected to antiviral activity tests in plaque reduction assays against HSV-1 and HSV-2. The hexane and EtOAc extracts from branches, and the hexane extract from leaves displayed the anti-herpes virus activities in the inactivation inhibition, while the EtOAc extract from leaves exhibited the anti-herpes virus activities in both inactivation treatment and post-inhibition (Table 1).Repeated chromatographies of the EtOAc extract of branches using the solvent systems of MeOH-CHCl 3 , acetone-hexane, and acetone-CHCl 3 led to the isolation of a new acridone alkaloid, glycosparvarine (1) Six acridone alkaloids including a new glycosparvarine (1), three limonoids, and four N-[(4-monoterpenyloxy)phenylethyl]-substituted sulfur-containing propanamide derivatives including two new species, (؉ ؉)-S-deoxydihydroglyparvin (10) and (؉ ؉)-S-deoxytetrahydroglyparvin (11), were isolated from the branches and the leaves of Glycosmis parva CRAIB collected in the east of Thailand. Antiviral activity evaluation of isolates against herpes simplex virus (HSV) type 1 and 2 disclosed that two acridone alkaloids, glycosparvarine (1) and glycofolinine (4), showed moderate inhibitory activities with 50% effective concentration (EC 50 ) of 348 m mM and 151 m mM, respectively; as well, (؉ ؉)-S-deoxydihydroglyparvin (10) exhibited anti-HSV activity at the lower concentration.