Synthesis and quantitative structure-activity relationship (QSAR) study of novel isoxazoline and oxime derivatives of podophyllotoxin as insecticidal agents.
In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, 33 isoxazoline and oxime derivatives of podophyllotoxin modified in the C and D rings were synthesized and their structures were characterized by Proton nuclear magnetic resonance ((1)H NMR), high-resolution mass spectrometry (HRMS), electrospray ionization-mass spectrometry (ESI-MS), optical rotation, melting point (mp), and infrared (IR) spectroscopy. The stereochemical configurations of compounds 5e, 5f, and 9f were unambiguously determined by X-ray crystallography. Their insecticidal activity was evaluated against the pre-third-instar larvae of northern armyworm, Mythimna separata (Walker), in vivo. Compounds 5e, 9c, 11g, and 11h especially exhibited more promising insecticidal activity than toosendanin, a commercial botanical insecticide extracted from Melia azedarach . A genetic algorithm combined with multiple linear regression (GA-MLR) calculation is performed by the MOBY DIGS package. Five selected descriptors are as follows: one two-dimensional (2D) autocorrelation descriptor (GATS4e), one edge adjacency indice (EEig06x), one RDF descriptor (RDF080v), one three-dimensional (3D) MoRSE descriptor (Mor09v), and one atom-centered fragment (H-052) descriptor. Quantitative structure-activity relationship studies demonstrated that the insecticidal activity of these compounds was mainly influenced by many factors, such as electronic distribution, steric factors, etc. For this model, the standard deviation error in prediction (SDEP) is 0.0592, the correlation coefficient (R(2)) is 0.861, and the leave-one-out cross-validation correlation coefficient (Q(2)loo) is 0.797.
Laboratory of Pharmaceutical Design and Synthesis, College of Sciences, Northwest Agriculture and Forestry (A&F) University , Yangling 712100, Shannxi, People's Republic of China.
Yi
Y
Wang
Yonghua
Y
Shao
Yangyang
Y
Wang
Lingling
L
Fan
Xiang
X
Yu
Xiaoyan
X
Zhi
Chun
C
Yang
Huan
H
Qu
Xiaojun
X
Yao
Hui
H
Xu
D000818:Animals; D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D007306:Insecticides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009036:Moths / Q000187:drug effects; D010091:Oximes / Q000737:chemistry; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D014315:Triterpenes
D004365:Drugs, Chinese Herbal; D007306:Insecticides; D010091:Oximes; D011034:Podophyllotoxin; C036454:toosendanin; D014315:Triterpenes