Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Computational Approaches for the Design of Mosquito Repellent Chemicals

Author(s): Subhash C. Basak* and Apurba K. Bhattacharjee*

Volume 27, Issue 1, 2020

Page: [32 - 41] Pages: 10

DOI: 10.2174/0929867325666181029165413

Price: $65

Abstract

Background: In view of many current mosquito-borne diseases there is a need for the design of novel repellents.

Objective: The objective of this article is to review the results of the researches carried out by the authors in the computer-assisted design of novel mosquito repellents.

Methods: Two methods in the computational design of repellents have been discussed: a) Quantitative Structure Activity Relationship (QSAR) studies from a set of repellents structurally related to DEET using computed mathematical descriptors, and b) Pharmacophore based modeling for design and discovery of novel repellent compounds including virtual screening of compound databases and synthesis of novel analogues.

Results: Effective QSARs could be developed using mathematical structural descriptors. The pharmacophore based method is an effective tool for the discovery of new repellent molecules.

Conclusion: Results reviewed in this article show that both QSAR and pharmacophore based methods can be used to design novel repellent molecules.

Keywords: Mosquito repellent, Quantitative Structure Activity Relationship (QSAR), Mathematical structural descriptors, Hierarchical QSAR, 3D Pharmacophore modeling, virtual screening, design and discovery of NCE (new chemical entity), Computer-assisted Molecular Modeling (CAMM).

« Previous Next »
[1]
(a) Mosquitoes could carry viral triple threat. Available at:. http://www.genengnews.com/gen-news-highlights/mosquitoes-could-carry-viral-triple-threat/81253435 (Accessed Date: 30 December 2019)
(b)WHO. WHO Director-General summarizes the outcome of the Emergency Committee regarding clusters of microcephaly and Guillain-Barre syndrome. World Health Organization. Available at: . https://www.who.int/news-room/detail/01-02-2016-who-director-general-summarizes-the-outcome-of-the-emergency-committee-regarding-clusters-of-microcephaly-and-guillain-barr%C3%A9-syndrome (Accessed Date: 30 December 2019)
(c)Gates Foundation awards Notre Dame $23 million for malaria,dengue studies, Available at: https://www.reuters.com/article/us-usa-indiana-notre-dame/gates-foundation-awards-notre-dame-23-million-for-malaria-dengue-studies-idUSBREA2D0YP20140314 (Accessed Date: 30 December 2019)
(d)Brewste, D. Mosquito: The story of mankind’s deadliest foe. Biomed. J., 2001, 323(7307), 289-290.
[2]
Kitchen, L.W.; Lawrence, K.L.; Coleman, R.E. The role of the United States military in the development of vector control products, including insect repellents, insecticides, and bed nets. J. Vector Ecol., 2009, 34(1), 50-61.
[http://dx.doi.org/10.1111/j.1948-7134.2009.00007.x] [PMID: 20836805]
[3]
(a)Koren, G.; Matsui, D.; Bailey, B. DEET-based insect repellents: safety implications for children and pregnant and lactating women. CMAJ, 2003, 169(3), 209-212.
[PMID: 12900480]
(b)Briassoulis, G.; Narlioglou, M.; Hatzis, T. Toxic encephalopathy associated with use of DEET insect repellents: a case analysis of its toxicity in children. Hum. Exp. Toxicol., 2001, 20(1), 8-14.
[http://dx.doi.org/10.1191/096032701676731093] [PMID: 11339626]
(c)Fradin, M.S. Mosquitoes and mosquito repellents: a clinician’s guide. Ann. Intern. Med., 1998, 128(11), 931-940.
[http://dx.doi.org/10.7326/0003-4819-128-11-199806010-00013] [PMID: 9634433]
[4]
Strickman, D. PMD (p-Menthane-3,8-Diol) and quwenling. In: Insect Repellents Principles, Methods, and Uses; Debboun, M.; Frances, S.P.; Strickman, D. Ed; Taylor & Francis (CRC Press): New York, 2006; p. 347.
[http://dx.doi.org/10.1201/9781420006650]
[5]
Available at:. http://www.epa.gov/REDs/factsheets/3105fact.pdf (Accessed July 6, 2005)
[6]
(a)Available at:. http://www.epnet.com.libproxy.lib.unc.edu (Accessed June 15, 2005).
(b)Available at:. http://www.ars-grin.gov/duke (Accessed June 23, 2005).
[7]
(a)Johnson, H.L.; Skinner, W.A.; Maibach, H.I.; Pearson, T.R. Repellent activity and physical properties of ring-substituted N,N-diethylbenzamides. J. Econ. Entomol., 1967, 60, 173-176.
[http://dx.doi.org/10.1093/jee/60.1.173]
(b)McIver, S.B. A model for the mechanism of action of the repellent DEET on Aedes aegypti (Diptera: Culicidae). J. Med. Entomol., 1981, 18(5), 357-361.
[http://dx.doi.org/10.1093/jmedent/18.5.357] [PMID: 7299789]
[8]
Klun, J.A.; Schmidt, W.F.; Debboun, M. Stereochemical effects in an insect repellent. J. Med. Entomol., 2001, 38(6), 809-812.
[http://dx.doi.org/10.1603/0022-2585-38.6.809] [PMID: 11761378]
[9]
Hansch, C.; Leo, A. Exploring QSARs: Fundamentals and Applications in Chemistry and Biology; American Chemical Society: Washington, D.C., 1995.
[10]
Basak, S.C. Mathematical descriptors for the prediction of property, bioactivity, and toxicity of chemicals from their structure: a chemical-cum-biochemical approach. Curr Comput Aided Drug Des, 2013, 9(4), 449-462.
[http://dx.doi.org/10.2174/15734099113096660041] [PMID: 24138422]
[11]
Basak, S.C.; Gute, B.D.; Grunwald, G.D. Relative effectiveness of topological, geometrical, and quantum chemical parameters in estimating mutagenicity of chemicals.QSAR in: Environmental Sciences - VII; Chen, F; Schuurmann, G., Ed.; SETAC Press: Pensacola, FL, 1997, pp. 245-261.
[12]
Basak, S. C.; Harriss, D. K.; Magnuson, V. R. POLLY ver 2.3, 1988, Copyright of the University of Minnesota.
[13]
Basak, S.C.; Grunwald, G.; Balaban, A. TRIPLET; Copyright of the University of Minnesota, 1993.
[14]
Molconn-Z Version 3.5; Hall Associates Consulting: Quincy, MA, 2000.
[15]
CambridgeSoft, Chem3D Ultra 8.0, Cambridge, MA, USA. , 2003.
[16]
Natarajan, R.; Basak, S.C.; Mills, D.; Kraker, J.J.; Hawkins, D.M. Quantitative structure-activity relationship modeling of mosquito repellents using calculated descriptors. Croat. Chem. Acta, 2008, 81(2), 333-340.
[17]
RAGON - Software for the calculation of molecular descriptors, Version 5.4, Todeschini, R.; Consonni, V.; Mauri, A. et al.; Talete srl.; Milan, Italy. 2006.
[18]
Majumdar, S.; Basak, S. C. Exploring intrinsic dimensionality of chemical spaces for robust QSAR model development: A comparison of several statistical approaches. Curr Comp-Aided drug Des., 2016, 12(4), 294-301.
[http://dx.doi.org/10.2174/1573409912666160906111821] [PMID: 27600878]
[19]
Hawkins, D.M.; Basak, S.C.; Mills, D. Assessing model fit by cross-validation. J. Chem. Inf. Comput. Sci., 2003, 43(2), 579-586.
[http://dx.doi.org/10.1021/ci025626i] [PMID: 12653524]
[20]
Kraker, J.J.; Hawkins, D.M.; Basak, S.C.; Natarajan, R.; Mills, D. Quantitative structure-activity relationship (QSAR) modeling of juvenile hormone activity: Comparison of validation procedures. Chemom. Intell. Lab. Syst., 2007, 87(1), 33-42.
[http://dx.doi.org/10.1016/j.chemolab.2006.03.001]
[21]
Suryanarayana, M.V.S.; Pandey, K.S.; Prakash, S.; Raghuveeran, C.D.; Dangi, R.S.; Swamy, R.V.; Rao, K.M. Structure-activity relationship studies with mosquito repellent amides. J. Pharm. Sci., 1991, 80(11), 1055-1057.
[http://dx.doi.org/10.1002/jps.2600801111] [PMID: 1687691]
[22]
Hawkins, D.M. LinMods; University of Minnesota: Minneapolis, MN, USA, 2004.
[23]
Devillers, J.; Lagneau, C.; Lattes, A.; Garrigues, J.C.; Clemente, M.M.; Yebakima, A. In silico models for predicting vector control chemicals targeting Aedes aegypti. SAR QSAR Environ. Res., 2014, 25(10), 805-835.
[http://dx.doi.org/10.1080/1062936X.2014.958291] [PMID: 25275884]
[24]
Garcia-Domenech, R.; Aguilera, J.; Moncef, A.E.; Pocovi, S.; Galvez, J. Application of molecular topology to the prediction of mosquito repellents of a group of terpenoid compounds. Mol. Divers., 2010, 14(2), 321-329.
[http://dx.doi.org/10.1007/s11030-009-9179-z] [PMID: 19578941]
[25]
Moore, S.J.; Debboun, M. History of insect repellents in: Insect Repellents: Principles, Methods, & Use. Strickman, D.; Frances, S.P; Debboun, M., Ed.; Taylor & Francis, CRC Press, 2006, pp. 3-29.
[26]
Skinner, W.A.; Johnson, H.I. The design of insect repellents. Drug Design, 1980, 10, 277-302.
[http://dx.doi.org/10.1016/B978-0-12-060310-7.50012-2]
[27]
(a)Kapetanovic, I.M. Computer-aided drug discovery and development (CADDD): in silico-chemico-biological approach. Chem. Biol. Interact., 2008, 171(2), 165-176.
[http://dx.doi.org/10.1016/j.cbi.2006.12.006] [PMID: 17229415]
(b)Kubinyi, H. Success stories of computer-aided design in: Computer Applications in Pharmaceutical Research and Development; Ekins, S; Wang, B., Ed.; Wiley-Interscience, 2006, pp. 377-424.
[http://dx.doi.org/10.1002/0470037237.ch16]
[28]
Podlogar, B.L.; Muegge, I.; Brice, L.J. Computational methods to estimate drug development parameters. Curr. Opin. Drug Discov. Devel., 2001, 4(1), 102-109.
[PMID: 11727315]
[29]
Leach, A.R.; Gillet, V.J.; Lewis, R.A.; Taylor, R. Three-dimensional pharmacophore methods in drug discovery. J. Med. Chem., 2010, 53(2), 539-558.
[http://dx.doi.org/10.1021/jm900817u] [PMID: 19831387]
[30]
Güner, O.F. Manual pharmacophore generation: visual pattern recognition In: Pharmacophore, perception, development, and use in drug design; O.F. Güner, Ed., University International Line (IUL Biotechnology Series), San Diego., 2000; pp. 17-20.
[31]
Bhattacharjee, A.K.; Hartell, M.G.; Nichols, D.A.; Hicks, R.P.P.; Stanton, B.; van Hamont, J.E.; Milhous, W.K. Structure-activity relationship study of antimalarial indolo [2,1-b]quinazoline-6,12-diones (tryptanthrins). Three dimensional pharmacophore modeling and identification of new antimalarial candidates. Eur. J. Med. Chem., 2004, 39(1), 59-67.
[http://dx.doi.org/10.1016/j.ejmech.2003.10.004] [PMID: 14987834]
[32]
Bhattacharjee, A.K.; Marek, E.; Le, H.T.; Gordon, R.K. Discovery of non-oxime reactivators using an in silico pharmacophore model of oxime reactivators of OP-inhibited acetylcholinesterase. Eur. J. Med. Chem., 2012, 49, 229-238.
[http://dx.doi.org/10.1016/j.ejmech.2012.01.016] [PMID: 22309910]
[33]
Temml, V.; Kaserer, T.; Kutil, Z.; Landa, P.; Vanek, T.; Schuster, D. Pharmacophore modeling for COX-1 and -2 inhibitors with LigandScout in comparison to Discovery Studio. Future Med. Chem., 2014, 6(17), 1869-1881.
[http://dx.doi.org/10.4155/fmc.14.114] [PMID: 25495981]
[34]
Studio, D. DS Version 2.5; Accelrys Inc.: San Diego, CA, 2007. Available at: http://accelrys.com/products/discovery-studio/ (Accessed Date: 30 December 2019)
[35]
Oliferenko, P.V.; Oliferenko, A.A.; Poda, G.I.; Osolodkin, D.I.; Pillai, G.G. Promising aedes aegypti repellent chemotypes identified through integrated QSAR, virtual screening, synthesis, and bioassay. PLoS One, 2013, 8(9)e64547
[http://dx.doi.org/ 10.1371/journal.pone.0064547] [PMID: 24039693]
[36]
Alcantara, E.P.E.P. In silico identification of potential inhibitors of dengue mosquito, Aedes aegypti chorion peroxidase. Comput. Biol. and Bioinform., 2014, 2(3), 38-42.
[http://dx.doi.org/10.11648/j.cbb.20140203.12]
[37]
Bhattacharjee, A.K.; Dheranetra, W.; Nichols, D.A.; Gupta, R.K. 3D pharmacophore model for insect repellent activity and discovery of new repellent candidates. QSAR Comb. Sci., 2005, 24, 593-602.
[http://dx.doi.org/10.1002/qsar.200430914]
[38]
Chemical Information System; Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring MD. U.S.A. Archives of the Chemical Information System, Division of Experimental Therapeutics, Washington, DC.,
[39]
Gupta, R.K.; Bhattacharjee, A.K.; Ma, D. 2011. US Patent: US7897162
[40]
Gupta, R.K.; Bhattacharjee, A.K. Discovery and design of new arthropod/insect repellents by computer-aided molecular modeling In: Insect repellents: principles, methods, and use; Press, C.R.C., Ed.; M. Debbon, S.P. Frances, and D. Strickman, Eds.; Press, C.R.C., Ed.; Taylor & Francis Group: Boca Raton, FL, 2006; pp. 195-228.
[41]
Bhattacharjee, A.K.; Gupta, R.K.; Ma, D.; Karle, J.M. Molecular similarity analysis between insect juvenile hormone and N, N-diethyl-m-toluamide (DEET) analogs may aid design of novel insect repellents. J. Mol. Recognit., 2000, 13(4), 213-220.
[http://dx.doi.org/10.1002/1099-1352(200007/08)13:4<213:AID-JMR500>3.0.CO;2-T] [PMID: 10931558]
[42]
Bhattacharjee, A.K. In silico stereoelectronic profile and pharmacophore similarity analysis of juvenile hormone, juvenile hormone mimics (IGRs) and insect repellents may aid discovery and design of novel arthropod repellents in: Juvenile hormones and juvenoids: Modeling biological effects and environmental fate devillers; Dr. J. ., Devillers., Ed.; CRC Press: Boca Raton, FL, 2013, pp. 297-331.
[http://dx.doi.org/10.1201/b14899-14]
[43]
Dheranetra, W.; Lawrence, K.L.; Benante, J.P.; Potter, M.A.; Chauhan, K.R.; Bathini, N.; White, C.E.; Mott, B.; Nichols, D.A.; Bhattacharjee, A.K.; Gupta, R.K. Comparative study of four membranes for evaluation of new insect/arthropod repellents using Aedes aegypti. In: Arthro-pod borne viral infections - current status and research; D. , Raghunath.; C.D., Rao, Eds.; Tata McGraw-Hill Compa-ny Ltd., 2008; pp. 418-424.
[44]
Bhattacharjee, A.K. In silico stereo-electronic analysis of PMD (p-Menthane-3-8-Diol) and its derivatives for pharmacophore development may aid discovery of novel insect repellents. Curr Comput Aided Drug Des (CCADD), 2013, 9(3), 308-316.
[http://dx.doi.org/10.2174/15734099113099990021] [PMID: 24010930]
[45]
Oliver, J.E.; Patterson, K.S. Wild ox bugs mosquitoes; C. & E. News, 2003, p. 49.
[46]
(a)Strickman, D. PMD (p-menthane-3,8-diol) and quwenling. In: Insect Repellents Principles, Methods, and Uses; Debboun, M.; Frances, S.P.; Strickman, D. Eds.; Taylor & Francis (CRC Press): New York., 2006; pp. 347-352.
(b)Bernier, U.R.; Kline, D.L.; Posey, K.H. Human emanations and related natural compounds that inhibit mosquito host-finding abilities In: Insect Repellents Principles, Methods, and Uses; Debboun, M.; Frances, S.P.; Strickman, D. Eds.; Taylor & Francis (CRC Press): New York, 2006; pp. 77-100.
[47]
Putz, M.V.; Dudas, N.A. Determining chemical reactivity driving biological activity from SMILES transformations: the bonding mechanism of anti-HIV pyrimidines. Molecules, 2013, 18(8), 9061-9116.
[http://dx.doi.org/10.3390/molecules18089061] [PMID: 23903183]
[48]
Balasubramanian, K.; Basak, S.C. Metabolic electron attachment as a primary mechanism for toxicity potentials of halocarbons. Curr. Comput. Aided Drug Des., 2016, 12(1), 62-72.
[http://dx.doi.org/10.2174/1573409912666160120151627] [PMID: 26787161]

Rights & Permissions Print Cite
Article Metrics
56
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy