Molecular Engineering of Curcumin, an Active Constituent of L. (Turmeric) of the Family with Improved Antiproliferative Activity.

Cancer is the world's second leading cause of death, accounting for nearly 10 million deaths and 19.3 million new cases in 2020. Curcumin analogs are gaining popularity as anticancer agents currently. We reported herein the isolation, molecular engineering, molecular docking, antiproliferative, and anti-epidermal growth factor receptor (anti-EGFR) activities of curcumin analogs. Three curcumin analogs were prepared and docked against the epidermal growth factor receptor (EGFR), revealing efficient binding. Antiproliferative activity against 60 NCI cancer cell lines was assessed using National Cancer Institute (NCI US) protocols. The compound , demonstrated promising antiproliferative activity in single dose (at 10 µM) as well as five dose (0.01, 0.10, 1.00, 10, and 100 µM). Compound inhibited leukemia cancer panel better than other cancer panels with growth inhibition of 50% (GI) values ranging from 1.48 to 2.73 µM, and the most promising inhibition with GI of 1.25 µM was observed against leukemia cell line SR, while the least inhibition was found against non-small lung cancer cell line NCI-H226 with GI value of 7.29 µM. Compounds , demonstrated superior antiproliferative activity than curcumin and gefitinib. In molecular docking, compound had the most significant interaction with four H-bonds and three π-π stacking, and compound was found to moderately inhibit EGFR. The curcumin analogs discovered in this study have the potential to accelerate the anticancer drug discovery program.