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Antimicrobial activity of newly synthesized thienoquinolizidines derivatives: inspired by natural plant alkaloids

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Abstract

The antimicrobial activity of 16 newly prepared quinolizidines derivatives using bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Proteus sp., Escherichia coli) acid fast bacterium Mycobacterium smegmatis, yeasts (Candida albicans, Candida parapsilosis), and filamentous fungi (Fusarium culmorum, Microsporum gypseum, Aspergillus flavus, Botrytis cinerea, Alternaria alternata) was studied in this paper. The best antibacterial properties were demonstrated by derivatives 11Ba, trans10Bb and 11Bb, and the most sensitive microorganism was found to be the gram-positive bacterium S. epidermidis. The derivative 11Bb showed the best antifungal activity, while C. albicans was resistant to all tested derivatives, and C. parapsilosis was fully inhibited in the presence of the derivative 11Ba and 11Bb. Among the filamentous fungi, only the dermatophyte M. gypseum was partially inhibited. Biofilms represent the most prevalent type of microbial growth in nature and are crucial to the development of clinical infections. Newly synthesized derivatives were also added into the medium throughout the biofilm formation. We have observed a significant decrease of biofilm formation in the presence of quinolizidine derivatives, testifying to their significant antimicrobial activity. It seems that the relationship between antimicrobial activity and the structure is based on the alkaline character due to nitrogen, the saturated basic quinolizidine skeleton, and the position of sulfur in the molecule.

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References

  • Atta-ur-Rahman A, Choudhary MI, Parvez K, Ahmed A, Akhtar F, Nur-E-Alam M, Hassan NM (2000) Quinolizidine alkaloids from Sophora alopecuroides. J Nat Prod 63:190–192. doi:10.3109/13880209.2013.767363

    Article  CAS  Google Scholar 

  • Baker DJ, Beddell CR, Champness JN, Goodford PJ, Morrngton FEA, Smith DR, Stammers DR (1981) The binding of trimethoprim to bacterial dihydrofolate reductases. FEBS Lett 126:49–52

    Article  CAS  Google Scholar 

  • Barczak AK, Hung DT (2009) Productive steps toward an antimicrobial targeting virulence. Curr Opin Microbiol 12:490–496. doi:10.1016/j.mib.2009.06.012

    Article  CAS  Google Scholar 

  • Blakley RL (1969) The biological reduction of pteridines. In: Neuberger A, Tatum EL (eds) The biochemistry of folic acid and related pteridines. North-Holland, Amsterdam, pp 139–187

    Google Scholar 

  • Clinical and Laboratory Standards Institute (CLSI) (1996) Reference method for broth dilution antifungal susceptibility testing yeast; approved standard. NCCLS document M27-A, 15, 10, VA Medical Center, Tucson

  • Clinical and Laboratory Standards Institute (CLSI). (2014) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; Approved standard—Eight edition, CLSI M7-A9, USA

  • Costerton JW, Lewandowski Z, Caldwell DE, Korber DR, Lappin-Scott HM (1995) Microbial biofilms. Ann Rev Microbiol 49:711–745. doi:10.1146/annurev.mi.49.100195.003431

    Article  CAS  Google Scholar 

  • Dankert J, Hogt A, Feijen J (1986) Biomedical polymers: bacterial adhesion, colonization, and infection. CRC Crit Rev Biocompat 2:219–301

    CAS  Google Scholar 

  • Ding PL, Liao ZX, Huang H, Zhou P, Chen DF (2006) (+)-12α-Hydroxysophocarpine, a new quinolizidine alkaloid and related anti-HBV alkaloids from Sophora flavescens. Bioorg Med Chem Lett 16:1231–1235. doi:10.1016/j.bmcl.2005.11.073

    Article  CAS  Google Scholar 

  • Dudová B, Hudecová D, Pokorný R, Mikulášová M, Palicová M, Segľa P, Melník M (2002) Copper complexes with bioactive ligands II. Antifungal activity. Folia Microbiol 47:225–229

    Article  Google Scholar 

  • Erdemoglu N, Ozkan S, Tosun F (2007) Alkaloid profile and antimicrobial activity of Lupinus angustifolius L. alkaloid extract. Phytochem Rev 6:197–201. doi:10.1007/s11101-006-9055-8

    Article  CAS  Google Scholar 

  • Erdemoglu N, Ozkan S, Duran A, Tosun F (2009) GC-MS analysis and antimicrobial activity of alkaloid extract from Genista vuralii. Pharm Biol 47:81–85. doi:10.1080/13880200802448674

    Article  CAS  Google Scholar 

  • Evans WC (2009) Alkaloids. In: Evans WC (ed) Trease and Evans’s pharmacognosy, 16th edn. Elsevier, Edinburgh, pp 353–415

    Chapter  Google Scholar 

  • Furlani RE, Yeagley AA, Melander C (2013) A flexible approach to 1,4-di-substituted 2-aminoimidazoles that inhibit and disperse biofilms and potentiate the effects of β-lactams against multi-drug resistant bacteria. Eur J Med Chem 62:59–70. doi:10.1016/j.ejmech.2012.12.005

    Article  CAS  Google Scholar 

  • Gellert E (1982) The indolizidine alkaloids. J Nat Prod 45:50–73. doi:10.1021/np50019a005

    Article  CAS  Google Scholar 

  • Guo B, Li C, Deng Z et al (2005) A new method for measurement of (−)-sophocarpine, a candidate therapeutic for viral myocarditis, in plasma: application to a toxicokinetic study in beagle dogs. Rapid Comm Mass Spectrom 19:2840–2888. doi:10.1002/rcm.2132

    Article  CAS  Google Scholar 

  • Hraiech S, Brégeon F, Brunel JM, Rolain JM, Lepidi H, Andrieu V, Roch A (2012) Antibacterial efficacy of inhaled squalamine in a rat model of chronic Pseudomonas aeruginosa pneumonia. J Antimicrob Chemother 67:2452–2458. doi:10.1093/jac/dks230

    Article  CAS  Google Scholar 

  • Huigens RW III, Rogers SA, Steinhauer AT, Melander C (2009) Inhibition of Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa biofilm formation with a class of TAGE–triazole conjugates. Org Biomol Chem 7:794–802. doi:10.1039/b817926c

    Article  CAS  Google Scholar 

  • Keisham SS, Babudal D, Chandrakant GN (2011) Quinolizidines alkaloids: Petrosin and xestospongins from the sponge Oceanapia sp. J Chem Sci 123(5):601–607

    Article  Google Scholar 

  • Kinghorn AD, Balandrin MF. (1984) Alkaloids: chemical and biological perspectives. In: Pelletier WS, (ed). Vol. 2, Wiley: New York, pp. 105–48

  • Kittakoop P, Mahidol C, Ruchirawat S (2014) Alkaloids as important scaffolds in therapeutic drugs for the treatments of cancer, tuberculosis, and smoking cessation. Curr Top Med Chem 14:239–252

    Article  CAS  Google Scholar 

  • Kornberg A, Baker TA (1992) Biosynthesis of DNA precursors. In: Kornberg A, Baker TA (eds) DNA Replication, 2nd edn. WH. Freeman and Company, New York, pp 53–100

    Google Scholar 

  • Küçükboyaci N, Özkan S, Adigüzel N, Tosun F (2011) Characterisation and antimicrobial activity of Sophora alopecuroides L. var. alopecuroides alkaloid extracts. Turk J Biol 35(3):379–385

    Google Scholar 

  • Majik MS, Naik D, Bhat C, Tilve S, Tilvi S, D’Souza L (2013) Synthesis of (R)-norbgugaine and its potential as quorum sensing inhibitor against Pseudomonas aeruginosa. Bioorg Med Chem Lett 23:2353–2356. doi:10.1016/j.bmcl.2013.02.051

    Article  CAS  Google Scholar 

  • O’Toole G, Kaplan HB, Kolter R (2000) Biofilm formation as microbial development. Annu Rev Microbiol 54:49–79. doi:10.1146/annurev.micro.54.1.49

    Article  Google Scholar 

  • Olejníková P, Birošová L, Švorc Ľ, Vihonská Z, Fiedlerová M, Marchalín Š, Šafář P (2015) Newly synthesized indolizine derivatives–antimicrobial and antimutagenic properties. Chem Pap 69(7):983–992. doi:10.1515/chempap-2015-0093

    Article  Google Scholar 

  • Rao KN, Venkatachalam SR (2000) Inhibition of dihydrofolate reductase and cell growth activity by the phenanthroindolizidine alkaloids pergularinine and tylophorinidine: the in vitro cytotoxicity of these plant alkaloids and their potential as antimicrobial and anticancer agents. Toxicol In Vitro 14(1):53–59

    Article  CAS  Google Scholar 

  • Robbers JE, Speedie MK, Tyler VE (1996) Alkaloids. In: Robbers JE, Speedie MK, Tyler VE (eds) Pharmacognosy and pharmacobiotechnology. Williams and Wilkins, London, pp 144–185

    Google Scholar 

  • Šafář P, Marchalín Š, Prónayová N, Vrábel V, Lawson AM, Othman M, Daïch A (2016) Use of chiral-pool approach into epi-thieno analogues of the scarce bioactive phenanthroquinolizidine alkaloids. Tetrahedron 72(23):3221–3231

    Article  Google Scholar 

  • Sen S, Kamma SR, Gundla R, Adepally U, Kuncha S, Thirnathi S, Prasad UV (2013) A reagent based DOS strategy via Evans chiral auxiliary: highly stereoselective Michael reaction towards optically active quinolizidinones, piperidinones and pyrrolidinones. RSC Adv 3(7):2404–2411. doi:10.1039/c2ra22115b

    Article  CAS  Google Scholar 

  • Shoichet BK, Stroud RM, Santi DV, Kuntz ID, Perry KM (1993) Structure-based discovery of inhibitors of thymidylate synthase. Science 259:1445–1450

    Article  CAS  Google Scholar 

  • Singh KS, Das B, Naik CG (2011) Quinolizidines alkaloids: Petrosin and xestospongins from the sponge Oceanapia sp. J Chem Sci 123(5):601–607. doi:10.1007/s12039-011-0124-1

    Article  CAS  Google Scholar 

  • Skogman ME, Kujala J, Busygin I, Leino R, Vuorela PM, Fallarero A (2012) Evaluation of antibacterial and anti-biofilm activities of cinchona alkaloid derivatives against Staphylococcus aureus. Nat Prod Commun 7:1173–1176

    CAS  Google Scholar 

  • Sparatore A, Veronese M, Sparatore F (1987) Quinolizidine derivatives with antimicrobial activity. Il Farm Ed Sci 42(3):159–174

    CAS  Google Scholar 

  • Taniguchi L, de Fátima Faria B, Rosa RT, e Carvalho ADP, Gursky LC, Elifio-Esposito SL, Parahitiyawa N, Samaranayak LP, Rosa EAR (2009) Proposal of a low-cost protocol for colorimetric semi-quantification of secretory phospholipase by Candida albicans grown in planktonic and biofilm phases. J Microbiol Methods 78(2):171–174. doi:10.1016/j.mimet.2009.05.012

    Article  CAS  Google Scholar 

  • Tyski S, Markiewicz M, Gulewicz K, Twardowski T (1988) The effect of lupine alkaloids and ethanol extracts from seeds of Lupinus angustifolius on selected bacterial strains. J Plant Physiol 133:240–242

    Article  CAS  Google Scholar 

  • Wang X, Yao X, Zhu Z, Tang T, Dai K, Sadovskaya I, Flahaut S, Jabbouri S (2009) Effect of berberine on Staphylococcus epidermidis biofilm formation. Int J Antimicrob Agents 34:60–66. doi:10.1016/j.ijantimicag.2008.10.033

    Article  Google Scholar 

  • Wink M (1988) Plant breeding: importance of plant secondary metabolites for protection against pathogens and herbivores. Theor Appl Gen 75:225–233

    Article  CAS  Google Scholar 

  • Wink M (1992) The role of quinolizidine alkaloids in plant insect interactions. In: Bernays EA (ed) Insect-plant interactions, vol IV. CRC Press, Boca Raton, pp 133–169

    Google Scholar 

  • Wink M (1993) Quinolizidine alkaloids. In: Waterman P (ed) Methods in plant biochemistry, vol 8. Academic Press, London, pp 197–239

    Google Scholar 

  • Wippich C, Wink M (1985) Biological properties of alkaloids. Influence of quinolizidine alkaloids and gramine on the germination and development of powdery mildew, Erysiphe graminis f. sp. hordei. Experientia 41:1477–1479

    Article  CAS  Google Scholar 

  • Zakrzewski SF (1963) The mechanism of binding of folate analogues by folate reductase. J Biol Chem 238:1485–1490

    CAS  Google Scholar 

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Acknowledgements

This work was supported by the Grant Agency of the Slovak Republic (Grant No. 1/0371/16). This contribution is also the result of the project: Research Center for Industrial Synthesis of Drugs, ITMS 26240220061, supported by the Research & Development Operational Program funded by the ERDF.

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Authors and Affiliations

  1. Faculty of Food and Chemical Technology, Institute of Biochemistry and Microbiology, Slovak University of Technology, Radlinského 9, 81237, Bratislava, Slovak Republic

    Petra Olejníková, Simon Thomay, Tomáš Pagáč & Zuzana Ježíková

  2. Faculty of Food and Chemical Technology, Institute of Organic Chemistry, Slovak University of Technology, Radlinského 9, 81237, Bratislava, Slovak Republic

    Štefan Marchalín & Peter Šafař

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  1. Petra Olejníková
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Correspondence to Petra Olejníková.

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Olejníková, P., Thomay, S., Pagáč, T. et al. Antimicrobial activity of newly synthesized thienoquinolizidines derivatives: inspired by natural plant alkaloids. Chem. Pap. 71, 2375–2383 (2017). https://doi.org/10.1007/s11696-017-0232-6

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