Design and synthesis of novel antifungal compounds bearing quinoline and thiophene moieties

PANG Lei; ZHAO Jing; NI Tingjunhong; ZANG Chengxu; DING Zichao; ZHANG Dazhi; JIANG Yuanying

doi:10.3969/j.issn.1006-0111.2017.01.005

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Objective Based on the structure-activity relationships on the reported antifungal agents bearing quinoline or thiophene moieties, novel compounds bearing both quinoline and thiophene were designed, synthesized, and evaluated for in vitro antifungal activity against Candida albicans. Methods With 5-cyanothiophene-2-carbaldehyde or 5-cyanothiophene-3-carbaldehyde as starting materials, 13 compounds were synthesized via reductive amination, reduction of cyano group and amidation of quinoline-or isoquinoline-carboxylic acid. Their chemical structures were characterized by ¹H NMR and MS. In vitro antifungal screening against Candida albicans SC5314 was performed with the microbroth dilution method. Results All the compounds exhibited potent antifungal activities against Candida albicans. Among them, compound 6k showed the highest antifungal activity with MIC₈₀ value of 0.5 μg/ml, which is same potent as fluconazole. Conclusion The designed compounds bearing both quinoline and thiophene exhibited potent antifungal activities, and deserve further research.

Design and synthesis of novel antifungal compounds bearing quinoline and thiophene moieties

1. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350112, China;School of Pharmacy, Second Military Medical University, Shanghai 200433, China

2. School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2016-10-08

Rev Recd Date: 2016-11-29

Key words:

Abstract: Objective Based on the structure-activity relationships on the reported antifungal agents bearing quinoline or thiophene moieties, novel compounds bearing both quinoline and thiophene were designed, synthesized, and evaluated for in vitro antifungal activity against Candida albicans. Methods With 5-cyanothiophene-2-carbaldehyde or 5-cyanothiophene-3-carbaldehyde as starting materials, 13 compounds were synthesized via reductive amination, reduction of cyano group and amidation of quinoline-or isoquinoline-carboxylic acid. Their chemical structures were characterized by ¹H NMR and MS. In vitro antifungal screening against Candida albicans SC5314 was performed with the microbroth dilution method. Results All the compounds exhibited potent antifungal activities against Candida albicans. Among them, compound 6k showed the highest antifungal activity with MIC₈₀ value of 0.5 μg/ml, which is same potent as fluconazole. Conclusion The designed compounds bearing both quinoline and thiophene exhibited potent antifungal activities, and deserve further research.

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[1]	Martín-Pe a A, Aguilar-Guisado M, Cisneros JM. Does the current treatment of invasive fungal infection need to be reviewed[J]. Enferm Infecc Microbiol Clin, 2014, 32(8):523-528.
[2]	Groll AH, Lumb J. New developments in invasive fungal disease[J]. Future Microbiol, 2012, 7(2):179-184.
[3]	Pfaller MA, Hata K, Jones RN, et al. In vitro activity of a novel broad-spectrum antifungal, E1210, tested against Candida spp. as determined by CLSI broth microdilution method[J]. Diagn Microbiol Infect Dis, 2011, 71(2):167-70.
[4]	Maebashi K, Kudoh M, Nishiyama Y, et al. A novel mechanism of fluconazole resistance associated with fluconazole sequestration in Candida albicans isolates from a myelofibrosis patient[J]. Microbiol Immunol, 2002, 46(5):317-326.
[5]	Jia XM, Wang Y, Jia Y, et al. RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in Candida albicans[J]. Cell Mol Life Sci, 2009, 66(1):122-34.
[6]	Espinel-Ingroff A, Pfaller M, Cantón E, et al. Emerging resistance to azoles and echinocandins:clinical relevance and laboratory detection[J]. Curr Fungal Infect Rep, 2010, 4(3):186-195.
[7]	Xia Lk, Idhayadhulla A, Lee YR, et al. Microwave-assisted synthesis of diverse pyrrolo[3,4-c]quinoline-1,3-diones and their antibacterial activities[J]. ACS Comb Sci, 2014, 16(7):333-341.
[8]	Musiol R, Serda M, Hensel-Bielowka S, et al. Quinoline-based antifungals[J]. Curr Med Chem, 2010, 17(18):1960-1973.
[9]	Chen M, Chen H, Ma JW, et al. Synthesis and anticancer activity of novel quinoline-docetaxel analogues[J]. Bioorg Med Chem Lett, 2014, 24(13):2867-2870.
[10]	Musiol R. Quinoline-based HIV integrase inhibitors[J]. Curr Pharm Des, 2013, 19(10):1835-1849.
[11]	Zuo R, Garrison AT, Basak A, et al. In vitro antifungal and antibiofilm activities of halogenated quinolone analogues against Candida albicans and Cryptococcus neoformans[J]. Int J Antimicrob Agents, 2016, 48(2):208-211.
[12]	Vandekerckhove S, Herreweghe SV, Willems J, et al. Synthesis of functionalized 3-, 5-, 6-and 8-aminoquinolines via intermediate (3-pyrrolin-1-yl)-and (2-oxopyrrolidin-1-yl)quinolones and evaluation of their antiplasmodial and antifungal activity[J]. Eur J Med Chem, 2015, 92(6):91-102.
[13]	Kouznetsov VV, Gómez CMM, Derita MG, et al. Synthesis and antifungal activity of diverse C-2 pyridinyl and pyridinylvinyl substituted quinolines[J]. Bioorg Med Chem, 2012, 20(21):6506-6512.
[14]	Vandekerckhove S, Tran HG, Desmet T, et al. Evaluation of (4-aminobutyloxy)quinolines as a novel class of antifungal agents[J]. Bioorg Med Chem Lett, 2013, 23(16):4641-4643.
[15]	Mohammad AIC, Satyendra D, Apurba T, et al. Synthesis and antimicrobial screening of some novel substituted thiophenes[J]. Hygeia, 2012, 4(1):112-118.
[16]	Scotti L, Scotti MT, Lima EO, et al. Experimental Methodologies and evaluations of computer-aided drug design methodologies applied to a series of 2-aminothiophene derivatives with antifungal activities[J]. Molecules, 2012, 17(3):2298-2315.
[17]	Mabkhot YN, Kaal NA, Alterary S, et al. Synthesis, In vitro antibacterial, antifungal, and molecular modeling of potent anti-microbial agents with a combined pyrazole and thiophene pharmacophore[J]. Molecules, 2015, 20(5):8712-8729.
[18]	Ajdacic V, Senerovic L, Vranic M, et al. Synthesis and evaluation of thiophene-based guanylhydrazones (iminoguanidines) efficient against panel of voriconazole-resistant fungal isolates[J]. Bioorg Med Chem, 2016, 24(6):1277-1291.
[19]	Guimar[AKa~D]es GP, Reis MYFA, Silva DTC, et al. Antifungal activity of topical microemulsion containing a thiophene derivative[J]. Braz J Microbiol, 2014, 45(2):545-550.

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Design and synthesis of novel antifungal compounds bearing quinoline and thiophene moieties

doi: 10.3969/j.issn.1006-0111.2017.01.005

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通讯作者: 陈斌, [email protected]

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