1,5-diaryl-3-oxo-1,4-pentadienes: a case for antineoplastics with multiple targets

Area of Science:

• Medicinal Chemistry
• Organic Chemistry
• Pharmacology

Background:

• The 1,5-diaryl-3-oxo-1,4-pentadienyl (dienone) moiety is present in organic molecules with antineoplastic properties.
• Attachment of the dienone moiety to various molecular scaffolds like piperidines and cycloalkanes has been explored.

Purpose of the Study:

• To review the antineoplastic properties of organic molecules containing the dienone moiety.
• To discuss the influence of physicochemical properties and molecular shape on cytotoxic potency.
• To highlight the potential of dienone-containing compounds as anticancer agents with multiple mechanisms of action.

Main Methods:

• Synthesis and characterization of dienone-containing compounds.
• Evaluation of cytotoxic activity against neoplastic and transformed cells (IC50 values).
• In vivo anticancer studies in rodent models.
• Computational analysis of physicochemical properties (redox potentials, logP, etc.) and molecular modeling.

Main Results:

• Many dienone compounds exhibit potent cytotoxicity (micromolar and nanomolar IC50 values).
• Some compounds show selective toxicity towards neoplastic cells over normal cells.
• Demonstrated in vivo anticancer efficacy and excellent tolerability in rodents.
• Physicochemical properties and molecular shape significantly influence antineoplastic activity.

Conclusions:

• The dienone moiety is a valuable structural unit for developing novel anticancer agents.
• Dienone compounds display diverse mechanisms of action, including apoptosis induction and mitochondrial respiration effects.
• These compounds possess additional beneficial properties such as anti-angiogenic and MDR-revertant activities.
• The dienone scaffold offers a promising platform for future anticancer drug design.