Synthesis, Characterization, and Pharmacological Evaluation of Curcumin Framework Employing a State-of-the-Art Computational Study Addressing Inflammatory Activities

Background: Curcumin, one of the main compounds of turmeric (Curcuma longa), has been extensively studied for its several bioactivities, notably antibacterial and antiinflammatory properties. However, the limited bioavailability of curcumin restricts its antibacterial and anti-inflammatory effectiveness. Thus, research on the design and synthesis of new curcumin derivatives is being pursued to enhance the efficacy. Aim: Our study aims to modify the 1, 3-dicarbonyl moiety of curcumin to improve its permanence as an anti-inflammatory and antibacterial mediator. Methods: Curcumin analogs (C1-C9) were synthesized and characterized by diverse spectroscopic techniques. Furthermore, the synthesized compounds were evaluated for their in vitro and in vivo anti-inflammatory and antibacterial activities. In addition to this, an in silico workup was carried out against the phospholipase A2 enzyme to confirm its anti-inflammatory profile. Results: The in vitro anti-inflammatory study revealed that the curcumin analogs, compounds C1, C3, C6, and C7, showed noteworthy inhibition at the 500 μg/ml concentration. Moreover, both acute and chronic in vivo anti-inflammatory activity showed a significant gradual decrease in paw thickness and a significant decrease in the weight of the cotton as compared to the standard drug, diclofenac. Besides, the in vitro antibacterial result showed a promising zone of inhibition for the compounds viz., C1, C2, C5, C6, and C7 at the concentration of 500 μg/ml, compared to the standard drug Amoxicillin, 250 μg/ml. In addition, the docking study reveals that curcumin analogs under observation, viz., C1, C2, C3, C6, and C7, had the highest binding affinity (-27.2249 to -21.1238 kcal/mol) with phospholipase A2 (PDB ID: 3U8I). Conclusion: In conclusion, the findings of this investigation indicate that synthesized curcumin derivatives are promising candidates for further investigation as therapeutic agents to control inflammatory- associated consequences.