Molecular Engineering of Curcumin, an Active Constituent of Curcuma longa L. (Turmeric) of the Family Zingiberaceae 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 3b,c demonstrated promising antiproliferative activity in single dose (at 10 mu M) as well as five dose (0.01, 0.10, 1.00, 10, and 100 mu M). Compound 3c inhibited leukemia cancer panel better than other cancer panels with growth inhibition of 50% (GI(50)) values ranging from 1.48 to 2.73 mu M, and the most promising inhibition with GI(50) of 1.25 mu M was observed against leukemia cell line SR, while the least inhibition was found against non-small lung cancer cell line NCI-H226 with GI(50) value of 7.29 mu M. Compounds 3b,c demonstrated superior antiproliferative activity than curcumin and gefitinib. In molecular docking, compound 3c had the most significant interaction with four H-bonds and three pi-pi stacking, and compound 3c was found to moderately inhibit EGFR. The curcumin analogs discovered in this study have the potential to accelerate the anticancer drug discovery program.

Automated summary

Cancer, as the second leading cause of death globally in 2020, has led to nearly 10 million deaths and 19.3 million new cases. Curcumin analogs are increasingly being recognized as promising anticancer agents. In this study, three curcumin analogs showed efficient binding to EGFR and demonstrated superior antiproliferative activity compared to curcumin and gefitinib, with compound 3c exhibiting the most significant interaction and inhibition against leukemia cells. These curcumin analogs have the potential to advance cancer drug discovery efforts.