Synthesis and biological evaluation of 2-phenyl-4-aminoquinolines as potential antifungal agents
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A series of 2-phenyl-4-aminoquinolines were designed, synthesized and evaluated for their antifungal activities against three phytopathogenic fungi in vitro. All of the target compounds were fully elucidated by 1H NMR, 13C NMR and HRMS spectra. The results indicated that most of the target compounds demonstrated significant activities against the tested fungi. Among them, compound 6e exhibited more promising inhibitory activities against C. lunata (EC50 = 13.3 μg/mL), P. grisea (EC50 = 14.4 μg/mL) and A. alternate (EC50 = 15.6 μg/mL), superior to azoxystrobin, a commercial agricultural fungicide. The structure–activity relationship (SAR) revealed that the aniline moiety at position 4 of the quinoline scaffold played a key role in the potency of a compound. And the substitution positions of the aniline moiety significantly influenced the activities. These encouraging results yielded a variety of 2-phenylquinolines bearing an aniline moiety acting as promising antifungal agents.
Keywords4-Aminoquinoline Phytopathogenic fungi Antifungal activity Structure–activity relationship
This work was funded by the National Natural Science Foundation of China (No. 31601670) and the Foundation of Education Department of Sichuan Province (No. 18ZB0079).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 5.Karekal MR, Biradar V, Bennikallu HMM (2013) Synthesis, characterization, antimicrobial, DNA cleavage, and antioxidant studies of some metal complexes derived from schiff base containing indole and quinoline moieties. Bioinorg Chem Appl 2013:315972. https://doi.org/10.1155/2013/315972 CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Emami S, Ghafouri E, Faramarzi MA, Samadi N, Irannejad H, Foroumadi A (2013) Mannich bases of 7-piperazinylquinolones and kojic acid derivatives: synthesis, in vitro antibacterial activity and in silico study. Eur J Med Chem 68:185–191. https://doi.org/10.1016/j.ejmech.2013.07.032 CrossRefPubMedGoogle Scholar
- 12.Qu TF, Qu LL, Wang XG, Xu T, Xiao X, Ding M, Deng L, Guo Y (2017) Design, synthesis, and antibacterial activity of novel 8-methoxyquinoline-2-carboxamide compounds containing 1,3,4-thiadiazole moiety. Zeitschrift für Naturforschung C 73(3–4):117–122. https://doi.org/10.1515/znc-2017-0063 CrossRefGoogle Scholar
- 15.Yaakov DB, Shadkchan Y, Albert N, Kontoyiannis DP, Osherov N (2017) The quinoline bromoquinol exhibits broad-spectrum antifungal activity and induces oxidative stress and apoptosis in Aspergillus fumigatus. J Antimicrob Chemother 72(8):2263–2272. https://doi.org/10.1093/jac/dkx117 CrossRefPubMedGoogle Scholar
- 18.Banu S, Bollu R, Naseema M, Gomedhika PM, Nagarapu L, Sirisha K, Kumar CG, Gundasw SK (2018) A novel templates of piperazinyl-1,2-dihydroquinoline-3-carboxylates: synthesis, anti-microbial evaluation and molecular docking studies. Bioorg Med Chem Lett 28(7):1166–1170. https://doi.org/10.1016/j.bmcl.2018.03.007 CrossRefPubMedGoogle Scholar
- 20.Vausselin T, Seron K, Lavie M, Mesalam AA, Lemasson M, Belouzard S, Feneant L, Danneels A, Rouille Y, Cocquerel L, Foquet L, Rosenberg AR, Wychowski C, Meuleman P, Melnyk P, Dubuisson J (2016) Identification of a new benzimidazole derivative as an antiviral against hepatitis C virus. J Virol 90(19):8422–8434. https://doi.org/10.1128/JVI.00404-16 CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Marvania B, Kakadiya R, Christian W, Chen TL, Wu MH, Suman S, Tala K, Lee TC, Shah A, Su TL (2014) The synthesis and biological evaluation of new DNA-directed alkylating agents, phenyl N-mustard-4-anilinoquinoline conjugates containing a urea linker. Eur J Med Chem 83:695–708. https://doi.org/10.1016/j.ejmech.2014.06.066 CrossRefPubMedGoogle Scholar
- 25.Abbas SH, Abd El-Hafeez AA, Shoman ME, Montano MM, Hassan HA (2019) New quinoline/chalcone hybrids as anti-cancer agents: design, synthesis, and evaluations of cytotoxicity and PI3 K inhibitory activity. Bioorg Chem 82:360–377. https://doi.org/10.1016/j.bioorg.2018.10.064 CrossRefPubMedGoogle Scholar
- 26.Meléndez Gómez CM, Kouznetsov VV, Sortino MA, Álvarez SL, Zacchino SA (2008) In vitro antifungal activity of polyfunctionalized 2-(hetero)arylquinolines prepared through imino Diels-Alder reactions. Bioorg Med Chem 16(17):7908–7920. https://doi.org/10.1016/j.bmc.2008.07.079 CrossRefPubMedGoogle Scholar
- 27.Liberto NA, Simoes JB, Silva SdP, da Silva CJ, Modolo LV, de Fatima A, Silva LM, Derita M, Zacchino S, Zuniga OMP, Romanelli GP, Fernandes SA (2017) Quinolines: microwave-assisted synthesis and their antifungal, anticancer and radical scavenger properties. Bioorg Med Chem 25(3):1153–1162. https://doi.org/10.1016/j.bmc.2016.12.023 CrossRefPubMedGoogle Scholar
- 28.Mudaliar S, Chikhalia KH, Shah NK (2016) Synthesis of 2-, 3- or 4-phenylsubtituted chalcones based on 4-phenylamino-6-nitro-2-[(E)-2-phenylvinyl]quinoline, evaluation of their antimicrobial and antifungal activity. Lett Drug Des Discovery 13(8):818–823. https://doi.org/10.2174/1570180812666151016205033 CrossRefGoogle Scholar
- 29.Montoya A, Quiroga J, Abonia R, Derita M, Sortino M, Ornelas A, Zacchino S, Insuasty B (2016) Hybrid molecules containing a 7-chloro-4-aminoquinoline nucleus and a substituted 2-pyrazoline with antiproliferative and antifungal activity. Molecules 21(8):969/1–969/19. https://doi.org/10.3390/molecules21080969 CrossRefGoogle Scholar
- 32.Pickard AJ, Liu F, Bartenstein TF, Haines LG, Levine KE, Kucera GL, Bierbach U (2014) Redesigning the DNA-targeted chromophore in platinum-acridine anticancer agents: a structure-activity relationship study. Chemistry 20(49):16174–16187. https://doi.org/10.1002/chem.201404845 CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Yang R, Gao ZF, Zhao JY, Li WB, Zhou L, Miao F (2015) New class of 2-aryl-6-chloro-3,4-dihydroisoquinolinium salts as potential antifungal agents for plant protection: synthesis, bioactivity and structure-activity relationships. J Agric Food Chem 63(7):1906–1914. https://doi.org/10.1021/jf505609z CrossRefPubMedGoogle Scholar