Structural development of curcumin: A natural product arsenal for diverse therapeutic targets- seizing opportunities through serendipity and rational design

•This review emphasizes the structural development of curcumin, highlighting how modifications and analogs of curcumin can be tailored for different therapeutic targets.•This contrasts with many other reviews that primarily discuss curcumin's natural properties and biological activities without delving deeply into its structural variations and the rationale behind these modifications.•The review uniquely addresses both serendipitous discoveries and rational design strategies in developing curcumin-based therapeutics.•The curcumin main scaffold was remain intact on the modification, the substitutions were made on its different positions.•While many reviews explore specific therapeutic applications (e.g., cancer, inflammation), this review provides a broad overview of curcumin's potential across a wide array of diseases and conditions, underlining its versatility as a therapeutic agent.•This review includes novel applications and emerging research areas that are often not covered in more narrowly focused reviews Curcumin, a polyphenolic compound found in turmeric, has demonstrated various therapeutic properties such as anti-inflammatory, antioxidant, and anti-cancer effects. However, its clinical application is limited by its poor bioavailability, which stems from its low solubility, rapid metabolism, and quick systemic elimination. Modifications in the chemical structure of curcumin have been employed to improve its pharmacokinetic properties. Incorporating various functional groups into the curcumin molecule can significantly impact its activity. Creating hybrid molecules by combining curcumin with other bioactive compounds can result in synergistic effects. The structural development of curcumin aims to enhance its therapeutic efficacy by improving its bioavailability, stability, and specific activity against various diseases. These new molecules could offer improved potency and target specific therapeutic areas more effectively. This review explores the serendipitous discoveries and rational design approaches that have contributed to curcumin's development as a potent therapeutic agent which can unlock a broader spectrum of therapeutic applications. [Display omitted]