Pharmacological Evaluation of Diclofenac Derivatives: A Comprehensive Review of Their Antibacterial, Anti-inflammatory, and Anticancer activities.

Abstract

Background: Diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), inhibits cyclooxygenase (COX), blocking the production of prostaglandins involved in inflammation, pain, and fever. Aim: Recent studies have focused on modifying diclofenac's molecular structure to enhance its pharmacological properties, particularly its antibacterial, anti-inflammatory, and anticancer activities. This review provides a comprehensive evaluation of diclofenac derivatives, focusing on biological activities and potential therapeutic applications. Methods: We describe the investigation of diclofenac sodium derivatives and their complexes, evaluating their potential biological uses through various spectroscopic techniques, including X-ray diffraction and infrared spectroscopy. A systematic literature search was conducted using databases such as PubMed, ScienceDirect, Web of Science, and Scopus from 2004 to 2024. Boolean operators were used to identify relevant studies on diclofenac derivatives and their biological activity. The inclusion criteria were peer-reviewed articles published in English that focused on diclofenac’s biological activities and novel therapeutic applications. A total of 22 articles were included in this review. Findings: Diclofenac derivatives have demonstrated enhanced pharmacological activities compared to the parent compound. The review highlights quantitative data such as IC50 values and enzyme inhibition rates for antibacterial, anti-inflammatory, and anticancer effects. For example, certain derivatives exhibited up to 5-fold greater COX-2 inhibition than diclofenac itself, with IC50 values as low as 0.05 µM. Additionally, diclofenac-metal complexes showed increased antibacterial activity with MIC values ranging from 0.1 to 0.5 µg/mL against multidrug-resistant bacterial strains. Conclusion: Diclofenac derivatives offer promising therapeutic potential beyond traditional NSAID applications. Their enhanced antibacterial, anti-inflammatory, and anticancer activities suggest potential in future drug development.