Abstract
Background: Oxime compounds, including oxime ethers and oxime esters, possess various biological activities. Many oxime ethers have been widely used in the fields of pesticides and medicines. However, oxime ethers are rarely used in the field of pesticides.
Methods: We chose the excellent fungicide pyrifenox as the lead compound, integrated pyridinyl, adamantyl and benzoyl moieties into one molecule, while also designed and synthesized ten 1- (adamantan-1-yl)ethanone oxime esters containing pyridinyl moiety. Moreover, we also evaluated their preliminary antifungal activities against S. sclerotiorum and B. cinerea.
Results: The target compounds were characterized by NMR, IR and HRMS. The preliminary bioactivity test showed that they exhibited some antifungal activity to S. sclerotiorum and B. cinerea, and EC50 values were in the range of 14.16-32.97 and 27.60-52.82 μg/mL, respectively.
Conclusion: Some target compounds such as 3d, 3e, 3h and 3i, exhibited moderate activities against S. sclerotiorum, with EC50 values of 14.16-18.18 μg/mL.
Keywords: Oxime ester, adamantane, pyridine, ketone, design, synthesis, antifungal activity.
Graphical Abstract
[1]
Grimmer, M.K.; van den Bosch, F.; Powers, S.J.; Paveley, N.D. Evaluation of a matrix to calculate fungicide resistance risk. Pest Manag. Sci., 2014, 70(6), 1008-1016.
[http://dx.doi.org/10.1002/ps.3646] [PMID: 24013934]
[http://dx.doi.org/10.1002/ps.3646] [PMID: 24013934]
[2]
Zhang, P.Z.; Wan, F.X.; Li, Y.; Li, C.K.; Jiang, L. Synthesis and antibacterial activity of novel ethyl 2-alkoxyimino-2-benzimidazol-2-yl acetates bearing a morpholine group. Res. Chem. Intermed., 2015, 41, 3349-3357.
[http://dx.doi.org/10.1007/s11164-013-1437-0]
[http://dx.doi.org/10.1007/s11164-013-1437-0]
[3]
Xiao, Y.S.; Yan, X.J.; Xu, Y.J.; Huang, J.X.; Yuan, H.Z.; Liang, X.M.; Zhang, J.J.; Wang, D.Q. Design, synthesis and fungicidal activity of 11-alkoxyimino-5,6-dihydro-dibenzo[b,e] azepine-6-one derivatives. Pest Manag. Sci., 2013, 69(7), 814-826.
[http://dx.doi.org/10.1002/ps.3440] [PMID: 23526747]
[http://dx.doi.org/10.1002/ps.3440] [PMID: 23526747]
[4]
Li, L.; Li, Z.; Wang, K.; Liu, Y.; Li, Y.; Wang, Q. Synthesis and antiviral, insecticidal, and fungicidal activities of gossypol derivatives containing alkylimine, oxime or hydrazine moiety. Bioorg. Med. Chem., 2016, 24(3), 474-483.
[http://dx.doi.org/10.1016/j.bmc.2015.08.015] [PMID: 26337022]
[http://dx.doi.org/10.1016/j.bmc.2015.08.015] [PMID: 26337022]
[5]
Hwang, T.L.; Wang, W.H.; Wang, T.Y.; Yu, H.P.; Hsieh, P.W. Synthesis and pharmacological characterization of 2-aminobenzaldehyde oxime analogs as dual inhibitors of neutrophil elastase and proteinase 3. Bioorg. Med. Chem., 2015, 23(5), 1123-1134.
[http://dx.doi.org/10.1016/j.bmc.2014.12.056] [PMID: 25650311]
[http://dx.doi.org/10.1016/j.bmc.2014.12.056] [PMID: 25650311]
[6]
Liu, A.; Ou, X.; Huang, M.; Wang, X.; Liu, X.; Wang, Y.; Chen, C.; Yao, J. Synthesis and insecticidal activities of novel oxime ether pyrethroids. Pest Manag. Sci., 2005, 61(2), 166-170.
[http://dx.doi.org/10.1002/ps.947] [PMID: 15619716]
[http://dx.doi.org/10.1002/ps.947] [PMID: 15619716]
[7]
Mitchell, G.; Clarke, E.D.; Ridley, S.M.; Gillen, K.J.; Vohra, S.K.; Greenhow, D.T. Synthesis and characterisation of some 4-keto derivatives of 1,3,4(2H)-isoquinolinetrione redoxmediator herbicides. Pest Manag. Sci., 2000, 56, 127-132.
[http://dx.doi.org/10.1002/(SICI)1526-4998(200002)56:2<127: AID-PS113>3.0.CO;2-L]
[http://dx.doi.org/10.1002/(SICI)1526-4998(200002)56:2<127: AID-PS113>3.0.CO;2-L]
[8]
Harini, S.T.; Kumar, H.V.; Rangaswamy, J.; Naik, N. Synthesis, antioxidant and antimicrobial activity of novel vanillin derived piperidin-4-one oxime esters: Preponderant role of the phenyl ester substituents on the piperidin-4-one oxime core. Bioorg. Med. Chem. Lett., 2012, 22(24), 7588-7592.
[http://dx.doi.org/10.1016/j.bmcl.2012.10.019] [PMID: 23116886]
[http://dx.doi.org/10.1016/j.bmcl.2012.10.019] [PMID: 23116886]
[9]
Xia, L.J.; Wang, X.B.; Xie, Y.; Wang, X.Y.; Xiao, W.; Zhong, X.M.; Huang, M.G.; Xue, W. Synthesis and biological activity of novel 1,4-pentadien-3-one oxime esters bearing ehterocycle moiety. Chin. J. Appl. Chem., 2017, 34, 316-323.
[http://dx.doi.org/10.11944/j.issn.1000-0518.2017.03.160219]
[http://dx.doi.org/10.11944/j.issn.1000-0518.2017.03.160219]
[10]
Xu, X.J.; Guo, J.X.; Zhu, D.Y.; Zhong, X. Synthesis of symmetrical disubstituted bridgehead adamantane derivatives. Chem. J. Chin. Univ., 2014, 35, 1686-1690.
[http://dx.doi.org/10.7503/cjcu20140051]
[http://dx.doi.org/10.7503/cjcu20140051]
[11]
Wanka, L.; Iqbal, K.; Schreiner, P.R. The lipophilic bullet hits the targets: Medicinal chemistry of adamantane derivatives. Chem. Rev., 2013, 113(5), 3516-3604.
[http://dx.doi.org/10.1021/cr100264t] [PMID: 23432396]
[http://dx.doi.org/10.1021/cr100264t] [PMID: 23432396]
[12]
El-Emam, A.A.; Al-Deeb, O.A.; Al-Omar, M.; Lehmann, J. Synthesis, antimicrobial, and anti-HIV-1 activity of certain 5-(1-adamantyl)-2-substituted thio-1,3,4-oxadiazoles and 5-(1-adamantyl)-3-substituted aminomethyl-1,3,4-oxadiazoline-2-thiones. Bioorg. Med. Chem., 2004, 12(19), 5107-5113.
[http://dx.doi.org/10.1016/j.bmc.2004.07.033] [PMID: 15351394]
[http://dx.doi.org/10.1016/j.bmc.2004.07.033] [PMID: 15351394]
[13]
Ali, A.G.; Mohamed, M.F.; Abdelhamid, A.O.; Mohamed, M.S. A novel adamantane thiadiazole derivative induces mitochondria-mediated apoptosis in lung carcinoma cell line. Bioorg. Med. Chem., 2017, 25(1), 241-253.
[http://dx.doi.org/10.1016/j.bmc.2016.10.040] [PMID: 27847140]
[http://dx.doi.org/10.1016/j.bmc.2016.10.040] [PMID: 27847140]
[14]
Su, X.; Pradaux-Caggiano, F.; Vicker, N.; Thomas, M.P.; Halem, H.; Culler, M.D.; Potter, B.V.L. Adamantyl ethanone pyridyl derivatives: Potent and selective inhibitors of human 11β-hydroxysteroid dehydrogenase type 1. ChemMedChem, 2011, 6(9), 1616-1629.
[http://dx.doi.org/10.1002/cmdc.201100182] [PMID: 21714097]
[http://dx.doi.org/10.1002/cmdc.201100182] [PMID: 21714097]
[15]
Kouatly, O.; Geronikaki, A.; Kamoutsis, C.; Hadjipavlou-Litina, D.; Eleftheriou, P. Adamantane derivatives of thiazolyl-N-substituted amide, as possible non-steroidal anti-inflammatory agents. Eur. J. Med. Chem., 2009, 44(3), 1198-1204.
[http://dx.doi.org/10.1016/j.ejmech.2008.05.029] [PMID: 18603333]
[http://dx.doi.org/10.1016/j.ejmech.2008.05.029] [PMID: 18603333]
[16]
Al-Wahaibi, L.H.; Hassan, H.M.; Abo-Kamar, A.M.; Ghabbour, H.A.; El-Emam, A.A. Adamantane-Isothiourea hybrid derivatives: Synthesis, characterization, in vitro antimicrobial, and in vivo hypoglycemic activities. Molecules, 2017, 22(5), 710-781.
[http://dx.doi.org/10.3390/molecules22050710] [PMID: 28468231]
[http://dx.doi.org/10.3390/molecules22050710] [PMID: 28468231]
[17]
Wang, B.L.; Shi, Y.X.; Zhang, S.J.; Ma, Y.; Wang, H.X.; Zhang, L.Y.; Wei, W.; Liu, X.H.; Li, Y.H.; Li, Z.M.; Li, B.J. Syntheses, biological activities and SAR studies of novel carboxamide compounds containing piperazine and arylsulfonyl moieties. Eur. J. Med. Chem., 2016, 117, 167-178.
[http://dx.doi.org/10.1016/j.ejmech.2016.04.005] [PMID: 27092414]
[http://dx.doi.org/10.1016/j.ejmech.2016.04.005] [PMID: 27092414]
[18]
Fu, C.W.; Hsieh, Y.J.; Chang, T.T.; Chen, C.L.; Yang, C.Y.; Liao, A.; Hsiao, P.W.; Li, W.S. Anticancer efficacy of unique pyridine-based tetraindoles. Eur. J. Med. Chem., 2015, 104, 165-176.
[http://dx.doi.org/10.1016/j.ejmech.2015.09.032] [PMID: 26457743]
[http://dx.doi.org/10.1016/j.ejmech.2015.09.032] [PMID: 26457743]
[19]
Li, T.; Zhang, J.; Pan, J.; Wu, Z.; Hu, D.; Song, B. Design, synthesis, and antiviral activities of 1,5-benzothiazepine derivatives containing pyridine moiety. Eur. J. Med. Chem., 2017, 125, 657-662.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.069] [PMID: 27721151]
[http://dx.doi.org/10.1016/j.ejmech.2016.09.069] [PMID: 27721151]
[20]
Liu, X.H.; Zhao, W.; Shen, Z.H.; Xing, J.H.; Yuan, J.; Yang, G.; Xu, T.M.; Peng, W.L. Synthesis, nematocidal activity and docking study of novel chiral 1-(3-chloropyridin-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives. Bioorg. Med. Chem. Lett., 2016, 26(15), 3626-3628.
[http://dx.doi.org/10.1016/j.bmcl.2016.06.004] [PMID: 27301365]
[http://dx.doi.org/10.1016/j.bmcl.2016.06.004] [PMID: 27301365]
[21]
Liu, X.H.; Zhai, Z.W.; Xu, X.Y.; Yang, M.Y.; Sun, Z.H.; Weng, J.Q.; Tan, C.X.; Chen, J. Facile and efficient synthesis and herbicidal activity determination of novel 1,2,4-triazolo[4,3-a]pyridin-3(2H)-one derivatives via microwave irradiation. Bioorg. Med. Chem. Lett., 2015, 25(23), 5524-5528.
[http://dx.doi.org/10.1016/j.bmcl.2015.10.064] [PMID: 26522951]
[http://dx.doi.org/10.1016/j.bmcl.2015.10.064] [PMID: 26522951]
[22]
Guan, A.Y.; Liu, C.L.; Sun, X.F.; Xie, Y.; Wang, M.A. Discovery of pyridine-based agrochemicals by using Intermediate Derivatization Methods. Bioorg. Med. Chem., 2016, 24(3), 342-353.
[http://dx.doi.org/10.1016/j.bmc.2015.09.031] [PMID: 26481150]
[http://dx.doi.org/10.1016/j.bmc.2015.09.031] [PMID: 26481150]
[23]
Wang, S.; Wan, F.; Liu, S.; Zhang, S.; Jiang, L. Synthesis and antifungal activity evaluation of novel substituted pyrimidine-5-carboxamides bearing the pyridine moiety. J. Chin. Chem. Soc. (Taipei), 2018, 65, 445-451.
[http://dx.doi.org/10.1002/jccs.201700310]
[http://dx.doi.org/10.1002/jccs.201700310]
[24]
Zhang, J.H.; Niu, L.Z.; Li, Y.; Liu, S.; Jiang, L. Facile synthesis of 2-(pyridin-3-yl)-2-benzoyloxyacet amides via Passerini reaction and evaluation of their biological activity. Youji Huaxue, 2018, 38, 1842-1848.
[http://dx.doi.org/10.6023/cjoc201801019]
[http://dx.doi.org/10.6023/cjoc201801019]
[25]
Sun, J.L.; Mu, W. Pesticide Science Experimental Techniquesand Guidance; Chemical Industry Press: Beijing, 2009.
[26]
Dolušić, E.; Larrieu, P.; Blanc, S.; Sapunaric, F.; Pouyez, J.; Moineaux, L.; Colette, D.; Stroobant, V.; Pilotte, L.; Colau, D.; Ferain, T.; Fraser, G.; Galleni, M.; Frère, J.M.; Masereel, B.; Van den Eynde, B.; Wouters, J.; Frédérick, R. Discovery and preliminary SARs of keto-indoles as novel indoleamine 2,3-dioxygenase (IDO) inhibitors. Eur. J. Med. Chem., 2011, 46(7), 3058-3065.
[http://dx.doi.org/10.1016/j.ejmech.2011.02.049] [PMID: 21419531]
[http://dx.doi.org/10.1016/j.ejmech.2011.02.049] [PMID: 21419531]
[27]
Karakurt, A.; Dalkara, S.; Özalp, M.; Özbey, S.; Kendi, E.; Stables, J.P. Synthesis of some 1-(2-naphthyl)-2-(imidazole-1-yl)ethanone oxime and oxime ether derivatives and their anticonvulsant and antimicrobial activities. Eur. J. Med. Chem., 2001, 36(5), 421-433.
[http://dx.doi.org/10.1016/S0223-5234(01)01223-5] [PMID: 11451531]
[http://dx.doi.org/10.1016/S0223-5234(01)01223-5] [PMID: 11451531]
Article Metrics
15