Synthesis, biological activities and structure-activity relationships for new avermectin analogues.
In an effort to discover new molecules with good insecticidal activities, more than 40 new avermectin derivatives were synthesized and evaluated for their biological activities against three species of arachnids, insects and nematodes, namely, Tetranychus Cinnabarinus, Aphis craccivora and Bursaphelenchus xylophilus. All the tested compounds showed potent inhibitory activities against three insect species. Notably, the majority of compounds exhibited high selectivity against T. cinnabarinus, some of which were much better in comparison with avermectin. Especially compounds 9j (LC50: 0.005 μM) and 16d (LC50: 0.002 μM) were 2.5- and 4.7-fold more active than avermectin (LC50: 0.013 μM), respectively, against T. cinnabarinus. Moreover, compounds 9b, 9d-f, 9h, 9j, 9l, 9n, 9p, 9r, 9v and 17d showed superior activities with LC50 values of 2.959-5.013 μM compared to that of 1 (LC50: 6.746 μM) against B. xylophilus. Meanwhile, the insecticidal activities of compounds 9f, 9g, 9h, and 9m against A. craccivora were 7-8 times better than that of avermectin, with LC50 values of 7.744, 5.634, 6.809, 7.939 and 52.234 μM, respectively. Furthermore, QSAR analysis showed that the molecular shape, size, connectivity degree and electronic distribution of avermectin analogues had substantial effects on insecticidal potency. These preliminary results provided useful insight in guiding further modifications of avermectin in the development of potential new insecticides.
School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
Jian
J
Zhang
School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
Xiang
X
Nan
Institute of Plant Protection, Gansu Academy of Agricultural Sciences, Lanzhou, 730070, China.
Hai-Tao
HT
Yu
School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
Pi-Le
PL
Cheng
School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
Yan
Y
Zhang
School of Pharmacy, Lanzhou University, Lanzhou, 730000, China. Electronic address: yqliu@lzu.edu.cn.
Ying-Qian
YQ
Liu
Provincial Engineering Laboratory of Biopesticide Preparation, Zhejiang A&F University, Lin'an, 311300, Zhejiang Province, China.
Shao-Yong
SY
Zhang
Institute of Plant Protection, Gansu Academy of Agricultural Sciences, Lanzhou, 730070, China.
Guan-Fang
GF
Hu
School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
Huanxiang
H
Liu
Provincial Engineering Laboratory of Biopesticide Preparation, Zhejiang A&F University, Lin'an, 311300, Zhejiang Province, China.
An-Liang
AL
Chen
D000818:Animals; D000969:Antinematodal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D009348:Nematoda / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship
D000969:Antinematodal Agents; D007559:Ivermectin; C019264:avermectin
Avermectin; Insecticidal activities; QSAR analysis; Structural modifications