Tyrosinase inhibitory pentacyclic Triterpenes and analgesic and spasmolytic activities of methanol extracts of Rhododendron collettianum

During the course of screening of medicinal plants of Pakistan for the isolation and structure elucidation of bioactive natural products, it was found that the methanol extract of the Rhododendron collettianum showed analgesic and spasmolytic activities. The methanol extract was then extracted with chloroform. Nine pentacyclic triterpenes were isolated from the chloroform extract and their structures were elucidated as erythrodiol (1), betulinic acid (2), maslinic acid (3), 2 alpha,3 alpha,23-trihydroxyolean-12-en-28-oic acid (4), bayogenin (5), arjunilic acid (6), methyl arjunolate (7), arjungenin (8) and 3 beta, 23, 24-trihydroxyolean-12-en-28-oic acid (9). Among the triterpenes (1-9) tested, arjunilic acid (6) was found to be most potent. Their structure-activity relationship (SAR) showed that if the configuration of the -OH group at C-2 is changed from alpha to beta the potency is decreased. In most of the compounds the position and configuration of the -OH group was found to be important for the inhibitory potency against the enzyme tyrosinase. For the comparison, the standard tyrosinase inhibitors kojfic acid (IC50 = 16.67 mu M) and L-mimosine (IC50 = 3.68 mu M) were used as controls. Copyright (c) 2007 John Wiley & Sons, Ltd.