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

Abstract

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-seco derivative (1b) moderately inhibited human immunodeficiency virus (HIV) protease (IC₅₀ 38.2 μM). The 2,2-dimethyl succinic acid (DMS) acylated tirucallane derivatives (4b, 6a, and 7b, 50 < IC₅₀ < 100 μM) were more inhibitory against HIV-1 PR than the others (PA, 2a, 4a, 4c–4d, 5a, 6b–6d, and 7a, 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.

Keywords:

• piscidinol A
• A-ring modified derivatives
• mono-acylated derivatives
• bi-acylated derivatives
• multi-acylated derivatives
• HIV-1 protease

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

This work was supported by the Guizhou provincial established project for modernizing medicine in the eleven five-year plan [grant number ZY (2011) 3003]; Undergraduate Innovation Training Program from Guiyang College of Traditional Chinese Medicine [grant number (2014) 36].