Thiazoline peptides and a tris-phenethyl urea from Didemnum molle with anti-HIV activity

J Nat Prod. 2012 Aug 24;75(8):1436-40. doi: 10.1021/np300270p. Epub 2012 Jul 30.

Abstract

As part of our screening for anti-HIV agents from marine invertebrates, the MeOH extract of Didemnum molle was tested and showed moderate in vitro anti-HIV activity. Bioassay-guided fractionation of a large-scale extract allowed the identification of two new cyclopeptides, mollamides E and F (1 and 2), and one new tris-phenethyl urea, molleurea A (3). The absolute configurations were established using the advanced Marfey's method. The three compounds were evaluated for anti-HIV activity in both an HIV integrase inhibition assay and a cytoprotective cell-based assay. Compound 2 was active in both assays with IC(50) values of 39 and 78 μM, respectively. Compound 3 was active only in the cytoprotective cell-based assay, with an IC(50) value of 60 μM.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / isolation & purification*
  • HIV Integrase Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Papua New Guinea
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / isolation & purification*
  • Peptides, Cyclic / pharmacology*
  • Phenylurea Compounds / chemistry
  • Phenylurea Compounds / isolation & purification*
  • Phenylurea Compounds / pharmacology*
  • Thiazolidines / chemistry
  • Thiazolidines / isolation & purification*
  • Thiazolidines / pharmacology*
  • Urochordata / chemistry*

Substances

  • HIV Integrase Inhibitors
  • Peptides, Cyclic
  • Phenylurea Compounds
  • Thiazolidines
  • mollamide E
  • mollamide F
  • molleurea A