Design, synthesis and structure-activity relationship of indoxacarb analogs as voltage-gated sodium channel blocker.
Indoxacarb, the first commercialized pyrazoline-type sodium-channel blocker, is a commonly used insecticide because of high selectivity. To discover sodium-channel blocker with high insecticidal activity, a series of novel indoxacarb analogs were designed and synthesized by judicious structural modifications of the substituent group of C5, C6 in indenone and C'4 in benzene ring. Some analogs exhibited significant insecticidal activities against Spodoptera litura F. and excellent BgNav1-1a channel inhibitory activity. The structure-activity analysis indicated that the presence of strong electron-withdrawing group and decreased steric hindrance of indenone ring (R(1), R(2)) in 5- and 6-position could enhance larvicidal activity and BgNav1-1a channel inhibitory activity.
State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Key Laboratory of Natural Pesticide and Chemical Biology, Ministry of Education, Laboratory of Insect Toxicology, South China Agricultural University, Guangzhou 510642, People's Republic of China; School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
Wenbo
W
Hao
State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Key Laboratory of Natural Pesticide and Chemical Biology, Ministry of Education, Laboratory of Insect Toxicology, South China Agricultural University, Guangzhou 510642, People's Republic of China.
Chunling
C
Fu
School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
Huijuan
H
Yu
School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
Jian
J
Chen
State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Key Laboratory of Natural Pesticide and Chemical Biology, Ministry of Education, Laboratory of Insect Toxicology, South China Agricultural University, Guangzhou 510642, People's Republic of China.
Hanhong
H
Xu
School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, People's Republic of China. Electronic address: shaog@mail.sysu.edu.cn.
Guang
G
Shao
State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Key Laboratory of Natural Pesticide and Chemical Biology, Ministry of Education, Laboratory of Insect Toxicology, South China Agricultural University, Guangzhou 510642, People's Republic of China. Electronic address: dxj2005@scau.edu.cn.
Dingxin
D
Jiang
D000818:Animals; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D007306:Insecticides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010078:Oxazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018411:Spodoptera / Q000187:drug effects*; D013329:Structure-Activity Relationship; D061567:Voltage-Gated Sodium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
D007306:Insecticides; D010078:Oxazines; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; C401104:indoxacarb
Indoxacarb analogs; Sodium channel blocker; Structure–activity relationships; Synthesis