Ali Amena, Ali Abuzer, Tahir Abu, Bakht Md Afroz, Ahsan Mohamed Jawed
Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Department of Pharmacognosy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Plants (Basel). 2021 Jul 29;10(8):1559. doi: 10.3390/plants10081559.
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.
癌症是全球第二大致死原因，2020年造成近1000万人死亡和1930万新发病例。姜黄素类似物作为抗癌药物目前正越来越受欢迎。我们在此报告了姜黄素类似物的分离、分子工程、分子对接、抗增殖和抗表皮生长因子受体（抗EGFR）活性。制备了三种姜黄素类似物并将其与表皮生长因子受体（EGFR）进行对接，显示出有效结合。使用美国国立癌症研究所（NCI US）的方案评估了对60种NCI癌细胞系的抗增殖活性。该化合物在单剂量（10μM）以及五剂量（0.01、0.10、1.00、10和100μM）下均表现出有前景的抗增殖活性。化合物对白血病癌症组的抑制作用优于其他癌症组，生长抑制率（GI）值范围为1.48至2.73μM，对白血病细胞系SR观察到最有前景的抑制作用，GI为1.25μM，而对非小细胞肺癌细胞系NCI-H226的抑制作用最小，GI值为7.29μM。化合物表现出比姜黄素和吉非替尼更强的抗增殖活性。在分子对接中，化合物与四个氢键和三个π-π堆积有最显著的相互作用，并且发现化合物适度抑制EGFR。本研究中发现的姜黄素类似物有潜力加速抗癌药物发现计划。
