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Mechanism of isoproturon resistance in Phalaris minor: in silico design, synthesis and testing of some novel herbicides for regaining sensitivity

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Abstract

Isoproturon, 3-p-cumenyl-1 dimethylurea was the only herbicide controlling Phalaris minor, a major weed growing in wheat fields till the early 1980s. Since it has acquired resistance against isoproturon, like other substituted urea herbicides, where the identified target site for isoproturon is in the photosynthetic apparatus at D1 protein of Photosystem-II (PS-II). Nucleotide sequence of susceptible and resistant psbA gene of P. minor has been reported to have four point mutations. During the present work D1 protein of both susceptible and resistant biotypes of P Minor has been modeled. Transmembrane segments of amino acids were predicted by comparing with the nearest homolog of bacterial D1 protein. Volume and area of active site of both susceptible and resistant biotypes has been simulated. Isoproturon was docked at the active site of both, susceptible and resistant D1 proteins. Modeling and simulation of resistance D1 protein indicates that the resistance is due to alteration in secondary structure near the binding site, resulting in loss in cavity area, volume and change in binding position, loss of hydrogen bonds, hydrophobic interaction and complete loss of hydrophobic sites. To regain sensitivity in resistant biotype new derivatives of isoproturon molecules have been proposed, synthesized and tested. Among the 17 derivatives we found that the N-methyl triazole substituted isoproturon is a potential substitute for isoproturon.

Isoproturon docking and receptor based pharmacophore of D1 protein susceptible (a) and resistant (b) shows loss of hydrophobic sites, explaining resistance, led to synthesis and pot assay of eighteen analogs of isoproturon.

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Acknowledgments

One of the authors (D. V. Singh) wishes to express his gratefulness to Prof. D. P. Misra, Ex-head, Biochemistry department, G. B. Pant University of Agriculture & Technology, Pantnagar, India for initiating the problem and to Prof. R. K. Malik, Director, Research Extension Education, Chaudhary Charan Singh Haryana Agricultural University, Hissar, Haryana, India for providing seeds of resistant & susceptible biotypes of P. minor. D. V. Singh would also like to thank Council of Scientific and Industrial Research (CSIR), Govt. of India for providing him a senior research fellowship. Another author (K.Adeppa) gratefully acknowledges the financial help and laboratory facilities made available to him by India Pesticide Limited, Lucknow, India

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Authors and Affiliations

  1. Indian Institute of Information Technology, Deoghat, Jhalwa, Allahabad, 211012, India

    Durg Vijay Singh

  2. Uttar Pradesh Technical University, Lucknow, 211026, India

    Kuruba Adeppa

  3. Center of Biomedical Magnetic Resonance SGPGIMS Campus, Raebareli Road, Lucknow, India

    Krishna Misra

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  1. Durg Vijay Singh
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  2. Kuruba Adeppa
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  3. Krishna Misra
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Correspondence to Krishna Misra.

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Singh, D.V., Adeppa, K. & Misra, K. Mechanism of isoproturon resistance in Phalaris minor: in silico design, synthesis and testing of some novel herbicides for regaining sensitivity. J Mol Model 18, 1431–1445 (2012). https://doi.org/10.1007/s00894-011-1169-2

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