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

J Asian Nat Prod Res. 2015;17(11):1079-90. doi: 10.1080/10286020.2015.1084505. Epub 2015 Oct 11.

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: A-ring modified derivatives; HIV-1 protease; bi-acylated derivatives; mono-acylated derivatives; multi-acylated derivatives; piscidinol A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • HIV Protease / drug effects*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship
  • Triterpenes / chemical synthesis*
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*

Substances

  • Anti-HIV Agents
  • Triterpenes
  • piscidinol A
  • tirucallane
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 1