Synthesis, Biological Activities, and Quantitative Structure–Activity Relationship (QSAR) Study of Novel Camptothecin Analogues

Molecules

Dan Wu²  Shao-Yong Zhang²  Ying-Qian Liu²  Xiao-Bing Wu²  Gao-Xiang Zhu¹  Yan Zhang¹  Wei Wei¹  Huan-Xiang Liu¹  An-Liang Chen² 

[1] School of Pharmacy, Lanzhou University, Lanzhou 730000, China; E-Mails:;Local and National Joint Engineering Laboratory of Biopesticide High-Efficient Preparation Technology, Zhejiang A&F University, Lin’an 311300, China; E-Mails:

关键词: camptothecin;    synthesis;    biological activity;    SAR analysis;    CoMFA;   

DOI  :  10.3390/molecules20058634

来源: mdpi

【 摘 要 】

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 andof 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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.