The quassinoids bruceines A-M: pharmacology, mechanism of action, synthetic advance, and pharmacokinetics-a review

Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec;397(12):9417-9433. doi: 10.1007/s00210-024-03281-7. Epub 2024 Jul 10.

Abstract

Bruceines A-L are among the quassinoid representatives found in the medicinal plant Brucea javanica (L.). An overview of their pharmacological activities is still unknown. The given research deals with highlights in their pharmacological result, molecular mechanism of action, synthetic progress, and pharmacokinetics. From previous evidence, bruceine derivatives are potential agents for anticancer treatments, as well as they are appropriate to treat inflammation, diabetes, and parasitic infections, and protect the neurons, kidneys, and lungs. Cytokine inhibitions, oxidative stress responses, and various signaling pathways, such as MAPK (mitogen-activated protein kinase) and NF-κB (nuclear factor-kappa B), have been proposed as the underlying mechanisms of action. Synthetic approaches to synthesize new derivatives with enhancement activities are based on free hydroxyl group modifications. Bruceines seem to be promptly absorbed by both oral and intravenous administrations, but their bioavailability is not high (less than 6%). Pre-clinical and clinical studies to prove their anticancer potential and other activities are urgent. Structural modifications, nano-combinations, and synergistic effects are necessary.

Keywords: Bruceine; Mechanism of action; Pharmacokinetics; Pharmacology; Synthesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Brucea / chemistry
  • Humans
  • Quassins* / chemistry
  • Quassins* / pharmacokinetics
  • Quassins* / pharmacology

Substances

  • Quassins
  • Antineoplastic Agents, Phytogenic