Abstract
The study on antitumor activities of artemisinin and its derivatives has been closely focused on in recent years. Herein, 2D and 3D QSAR analysis was performed on the basis of a series of artemisinin derivatives with known bioactivities against the non-small-cell lung adenocarcinoma A549 cells. Four QSAR models were successfully established by CoMSIA, CoMFA, topomer CoMFA and HQSAR approaches with respective characteristic values q2 = 0.567, R2 = 0.968, ONC = 5; q2 = 0.547, R2 = 0.980, ONC = 7; q2 = 0.559, R2 = 0.921, ONC = 7 and q2 = 0.527, R2 = 0.921, ONC = 6. The predictive ability of CoMSIA with r2 = 0.991 is the best one compared with the other three approaches, such as CoMFA (r2 = 0.787), topomer CoMFA (r2 = 0.819) and HQSAR (r2 = 0.743). The final QSAR models can provide guidance in structural modification of artemisinin derivatives to improve their anticancer activities.
Highlights
Cancer ranks the top public health threat and is the main cause of death in China [1]
37 artemisinin derivatives were randomly selected as a training set to generate Quantitative structure activity relationship (QSAR) models
It is assumed that four fields (A/H/S/E) from the comparative molecular similarity indices analysis (CoMSIA) model are more comprehensive than two fields (S/E) from comparative molecular field analysis (CoMFA) and topomerCoMFA models
Summary
Cancer ranks the top public health threat and is the main cause of death in China [1]. There are some pharmacokinetic limitations of artemisinin, such as low solubility in water or organic media, low bioavailability and short plasma half-life in vivo [8]. To overcome these problems, a series of artemisinin derivatives such as artemether, Artemisia ether, dihydroartemisinin, artesunate were designed to improve both antimalarial and anticancer activities [9]. PIC50 5.134 4.793 5.275 5.115 5.602 4.962 4.716 comparative molecular similarity indices analysis (CoMSIA) [10, 11], topomerCoMFA [12] and hologram QSAR (HQSAR) [13] was widely used in drug development process. Cheng and co-workers established CoMFA and CoMSIA models to study artemisinin and its analogues as antimalarial agents. Traditional QSAR, topomer QSAR and HQSAR based on 46 compounds against A549 cell were performed to get useful information to guide the structural modification of artemisinin for improvement of its antitumor activities
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