Design, Synthesis, Biological Evaluation, and In Silico Studies of Novel Multitarget Cinnamic Acid Hybrids

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Biochemistry

Background:

• Chronic inflammation is a key factor in multifactorial diseases like cancer and cardiovascular disorders.
• Cyclooxygenases (COXs) and lipoxygenases (LOXs) are crucial enzymes in the inflammatory process.
• Cinnamic acid hybrids with nitric oxide (NO) donors are emerging as potential therapeutic agents.

Purpose of the Study:

• To synthesize novel cinnamic acid-NO donor hybrids as multitarget agents.
• To evaluate their antioxidant, anti-inflammatory, and cytotoxic properties.
• To investigate their potential for treating inflammatory and multifactorial diseases.

Main Methods:

• Synthesis of cinnamic acid-NO donor hybrids (compounds 5a-i, 6a-i, 9a-i, 11).
• In vitro evaluation of lipid peroxidation, LOX, COX-1, and COX-2 inhibition.
• Assessment of NO release, albumin denaturation inhibition, and cytotoxicity against cancer cell lines.
• In silico studies were performed for all synthesized compounds.

Main Results:

• Compound 9a exhibited potent LOX inhibition, significant antioxidant activity, and high NO donor potency.
• Compound 9e showed dual inhibitory activity against COX-2 and LOX.
• Compound 6i displayed strong cytotoxic effects against multiple cancer cell lines (EC50: 36-45 μM).

Conclusions:

• Novel cinnamic acid-NO donor hybrids possess multitarget anti-inflammatory and potential anticancer properties.
• Compound 9a is a promising agent for inflammatory conditions due to its antioxidant and NO-releasing capabilities.
• Compounds 9e and 6i show potential as dual COX-LOX inhibitors and anticancer agents, respectively.