Biological evaluation of indolactams for in vitro bryostatin 1-like activity

UyenPhuong Tran; Kelvin L Billingsley

doi:10.1016/j.bmcl.2023.129570

Biological evaluation of indolactams for in vitro bryostatin 1-like activity

Bioorg Med Chem Lett. 2024 Jan 1:97:129570. doi: 10.1016/j.bmcl.2023.129570. Epub 2023 Nov 28.

Authors

UyenPhuong Tran¹, Kelvin L Billingsley²

Affiliations

¹ Department of Chemistry and Biochemistry, California State University Fullerton, Fullerton, CA 92831, USA.
² Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, IL 60660, USA. Electronic address: kbillingsley@luc.edu.

PMID: 38036273
DOI: 10.1016/j.bmcl.2023.129570

Abstract

Small molecule activators of protein kinase C (PKC) have traditionally been classified as either tumor promoters or suppressors. Although bryostatin 1 has well established anti-cancer activity, most natural products that target the PKC regulator domain exhibit tumor promotion properties. In this study, we examine a focused library of indolactam analogues in cell-based assays to establish the structural features of the scaffold that enhance bryostatin 1-like activity. These systematic biological assessments identified specific indole substitution patterns that impart diminished tumor promotion behavior in vitro for indolactam analogues, while still maintaining nanomolar potency for PKC.

Keywords: Bryostatin 1; Cancer; Cancer cell; Cell-based assays; Indolactam; Organic synthesis; Phorbol ester; Tumor promoter; Tumor suppressor; protein kinase C.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bryostatins / chemistry
Bryostatins / metabolism
Bryostatins / pharmacology
Humans
Lactams* / chemistry
Lactams* / pharmacology
Lactones
Neoplasms*
Protein Kinase C* / metabolism
Tetradecanoylphorbol Acetate

Substances

bryostatin 1
Bryostatins
Lactones
Protein Kinase C
Tetradecanoylphorbol Acetate
Lactams