title: Synthesis, biological activities, and quantitative structure-activity relationship (QSAR) study of novel camptothecin analogues.
abstract: In continuation of our program aimed at the development of natural product-based pesticidal agents, three series of novel camptothecin derivatives were designed, synthesized, and evaluated for their biological activities against T. Cinnabarinus, B. brassicae, and B. xylophilus. All of the derivatives showed good-to-excellent activity against three insect species tested, with LC50 values ranging from 0.00761 to 0.35496 mmol/L. Remarkably, all of the compounds were more potent than CPT against T. Cinnabarinus, and compounds 4d and 4c displayed superior activity (LC50 0.00761 mmol/L and 0.00942 mmol/L, respectively) compared with CPT (LC50 0.19719 mmol/L) against T. Cinnabarinus. Based on the observed bioactivities, preliminary structure-activity relationship (SAR) correlations were also discussed. Furthermore, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model using comparative molecular field analysis (CoMFA) was built. The model gave statistically significant results with the cross-validated q2 values of 0.580 and correlation coefficient r2 of 0.991 and  of 0.993. The QSAR analysis indicated that the size of the substituents play an important in the activity of 7-modified camptothecin derivatives. These findings will pave the way for further design, structural optimization, and development of camptothecin-derived compounds as pesticidal agents.
authors.affiliation: Local and National Joint Engineering Laboratory of Biopesticide High-Efficient Preparation Technology, Zhejiang A&F University, Lin'an 311300, China. wud2012@lzu.edu.cn.|School of Pharmacy, Lanzhou University, Lanzhou 730000, China. wud2012@lzu.edu.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Local and National Joint Engineering Laboratory of Biopesticide High-Efficient Preparation Technology, Zhejiang A&F University, Lin'an 311300, China. 1zhangshaoyong@163.com.
authors.forename: Shao-Yong
authors.initials: SY
authors.lastname: Zhang
authors.affiliation: Local and National Joint Engineering Laboratory of Biopesticide High-Efficient Preparation Technology, Zhejiang A&F University, Lin'an 311300, China. yqliu@lzu.edu.cn.|School of Pharmacy, Lanzhou University, Lanzhou 730000, China. yqliu@lzu.edu.cn.
authors.forename: Ying-Qian
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: Local and National Joint Engineering Laboratory of Biopesticide High-Efficient Preparation Technology, Zhejiang A&F University, Lin'an 311300, China. wuxb13@lzu.edu.cn.|School of Pharmacy, Lanzhou University, Lanzhou 730000, China. wuxb13@lzu.edu.cn.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China. zhugx13@lzu.edu.cn.
authors.forename: Gao-Xiang
authors.initials: GX
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Zhangyan10@lzu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China. WeiW13@lzu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China. hxliu@lzu.edu.cn.
authors.forename: Huan-Xiang
authors.initials: HX
authors.lastname: Liu
authors.affiliation: Local and National Joint Engineering Laboratory of Biopesticide High-Efficient Preparation Technology, Zhejiang A&F University, Lin'an 311300, China. anlchen@126.com.
authors.forename: An-Liang
authors.initials: AL
authors.lastname: Chen
mesh_terms: D000818:Animals; D001042:Aphids / Q000187:drug effects; D061046:Biological Control Agents / Q000737:chemistry*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry*; D007306:Insecticides / Q000737:chemistry*; D009348:Nematoda / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D040102:Tetranychidae / Q000187:drug effects
chemical_list: D061046:Biological Control Agents; D007306:Insecticides; D002166:Camptothecin
keywords: CoMFA; SAR analysis; biological activity; camptothecin; synthesis