Computer-guided design, synthesis, and protein kinase C affinity of a new salicylate-based class of bryostatin analogs

Org Lett. 2014 Oct 3;16(19):5136-9. doi: 10.1021/ol502491f. Epub 2014 Sep 19.

Abstract

Bryostatin 1 is in clinical trials for the treatment of cancer and Alzheimer's disease and is a candidate for a first-in-class approach to HIV/AIDS eradication. It is neither readily available nor optimally suited for clinical use. Using a function oriented synthesis strategy, a new class of bryostatin-inspired analogs was designed with a simplified salicylate-derived subunit, enabling step-economical synthesis (23 total steps) of agents exhibiting bryostatin-like affinity to protein kinase C (PKC).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bryostatins / chemical synthesis*
  • Bryostatins / chemistry
  • Bryostatins / pharmacology*
  • Humans
  • Molecular Structure
  • Protein Kinase C / drug effects*
  • Salicylates / chemical synthesis*
  • Salicylates / chemistry
  • Salicylates / pharmacology*

Substances

  • Bryostatins
  • Salicylates
  • bryostatin 1
  • Protein Kinase C