Benzisoxazolones: antimicrobial and antileukemic activity

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Pharmacology

Background:

• o-Nitrostyrene oxide undergoes acid-mediated rearrangement.
• Benzisoxazolone derivatives are explored for biological activities.

Purpose of the Study:

• To synthesize and evaluate a novel benzisoxazolone derivative and its analogues for antimicrobial and cytotoxic properties.
• To investigate the antipseudomonal activity of these compounds.

Main Methods:

• Acid-mediated rearrangement of o-nitrostyrene oxide.
• Synthesis of analogues via modified zinc-reduction of o-nitrobenzoate.
• Antimicrobial and cytotoxic activity assays.
• In vitro and in vivo antipseudomonal testing.

Main Results:

• 1-(hydroxymethyl)-2,1-benzisoxazol-3(1H)-one was synthesized and showed broad-spectrum antimicrobial and cytotoxic activity.
• Several analogues exhibited promising antipseudomonal activity in agar and broth diffusion assays.
• The synthesized analogues were ineffective in in vivo models of pseudomonal infection.

Conclusions:

• The novel benzisoxazolone scaffold possesses significant antimicrobial and cytotoxic potential.
• Further optimization is required to develop effective in vivo antipseudomonal agents from these analogues.