Synthesis, insecticidal activities and molecular docking studies on cis-nitenpyram analogues with a flexible amido segment anchored on tetrahydropyrimidine ring

Abstract

To make further studies on the difference of cis-nitenpyram analogues, a series of cis-nitenpyram compounds containing a flexible amido segment anchored on tetrahydropyrimidine ring was designed and synthesized. Preliminary bioassays indicate that all the analogues exhibit a mortality of 100% at 100 mg/L, and the analogue 4d shows the best activity against Nilaparvata lugens and Myzus persicae, with a mortality of 100% at 4 mg/L (LC₅₀=0.172 mg/L). The structure activity relationship studies show that insecticidal activities of the analogues are affected by the kinds and size of substituent R. In addition, the molecular docking simulations reveal that compouds 4 with a flexible amido segment on tetrahydropyrimidine ring show their different binding affinities for the nicotinic acetylcholine receptor(nAChR) of insect and compoud 4d shows stronger hydrogen-bonding with nAChR, which may provide the structure-activity relationship observed in vitro.

Keywords

cis-Nitenpyram analogue / Nicotinic acetylcholine receptor(nAChR) / Flexible amido segment / Hydrogen-bonding action / Structure activity relationship / Insecticidal activity / Molecular docking

References

[1] Kagabu S. Chemistry of Crop. Protection, Progress and Prospects in Science and Regulation, 2003, Weinheim: Wiley-VCH 193.

[2] Tomizawa M, Casida J E. Annu. Rev. Pharmacol. Toxicol., 2005, 45: 247.

[3] Matsuda K, Shimomura M, Ihara M, Akamatsu M, Sattelle D B. Biosci. Biotechnol. Biochem., 2005, 69: 1442.

[4] Jeschke P, Nauen R. Pest. Mana. Sci., 2008, 64: 1084.

[5] Tomizawa M, Talley T, Maltby D, Durkin K A, Medzihradszky K F, Burlingame A L, Taylor P, Casida J E. Proc. Natl. Acad. Sci. USA, 2007, 104: 9075.

[6] Kagabu S, Ishihara R, Nishimura K, Naruse Y. J. Agric. Food Chem., 2007, 55: 812.

[7] Nauen R, Denholm I. Arch. Insect. Biochem. Physiol., 2005, 58: 200.

[8] Nauen R, Elbert A. Pest. Manag. Sci., 2000, 56: 60.

[9] Sun C W, Yang D R, Xing J H, Wang H F, Jin J, Zhu J. J. Agric. Food. Chem., 2010, 58: 3415.

[10] Sun C W, Xu X, Xu Y H, Yang D R, Fang T, Liu T Y. J. Agric. Food. Chem., 2011, 59: 4828.

[11] Ma X B, Yin A Q, Xue S J. J. Shanghai Normal University (Natural Science), 2011, 40: 41.

[12] Huey R, Morris G M, Olson A J. J. Comput. Chem., 2007, 28: 1145.

[13] Ihara M, Okajima T, Yamashita A. Invert. Neurosci., 2008, 8: 71.

[14] Zhao P L, Wang F, Zhang Z M. J. Agric. Food Chem., 2008, 56: 10767.

[15] Abbott W S. J. Econ. Entomol., 1995, 18: 265.

[16] Wei T, Shi Y F. Tetrahedron Letters, 2008, 49: 6003.

[17] Wang D S. Pesticide, 2002, 41: 43.

[18] Isao M, Koichi I, Tetsuo O. Alpha-Unsaturated Amines Their Production and Use, 1989, EP0302389A2.