Synthesis of piscidinol A derivatives and their ability to inhibit HIV-1 protease.

Four types of piscidinol A derivatives were synthesized and evaluated their ability to inhibit HIV-1 protease to understand their structure-activity relationships. Of these tirucallane-type triterpene derivatives, an A-secoderivative (1b) moderately inhibited human immunodeficiency virus (HIV) protease (IC5038.2 μM). The 2,2-dimethyl succinic acid (DMS) acylated tirucallane derivatives (4b,6a,and7b, 50 < IC50 < 100 μM) were more inhibitory against HIV-1 PR than the others (PA,2a,4a,4c–4d,5a,6b–6d,and7a, IC50 > 100 μM). These findings indicated that the 2,3-seco-2,3-dioic acid (1b) and DMS-acylated tirucallane-type derivatives preferably inhibited HIV viral protease. [ABSTRACT FROM PUBLISHER]