Medicinal Chemistry Research

, Volume 27, Issue 3, pp 980–988 | Cite as

Antimicrobial and cytotoxic activities of short carbon chain unsaturated sucrose esters

  • Krasimira T. Petrova
  • M. Teresa Barros
  • Ricardo C. Calhelha
  • Marina Soković
  • Isabel C. F. R. Ferreira
Original Research
  • 132 Downloads

Abstract

A library of C3–C5 unsaturated 6-O-sucrose esters have been investigated for their antibacterial, antifungal, and cytotoxic activities. Most of the target compounds showed good inhibitory activity against a variety of clinically and food contaminant important microbial pathogens. In particular, 6-O-methacryloyl sucrose 2 and 1′,2,3,3′,4,4′,6′-hepta-O-acetyl-6-O-methacryloyl sucrose 9 were the most active bactericides against all the tested bacteria with minimal inhibitory concentrations (MICs) ranging between 0.24 and 1.40 μM. The compound 9 showed also the highest antifungal activity with MICs from 0.28 to 1.10 μM. The synthesized compounds possessed low cytotoxicity against human breast, lung, cervical, and hepatocellular carcinoma cell lines without showing toxicity for non-tumor liver cells. Thus, this library of short carbon chain unsaturated sucrose esters represent promising leads for the development of new generation of sucrose-based antimicrobial agents.

Keywords

Unsaturated esters Sucrose Antibacterial activity Antifungal activity Cytotoxic activity 

Notes

Acknowledgements

This work has been supported by Fundação para a Ciência e a Tecnologia through grant nos. PEst-C/EQB/LA0006/2013 and PEst-OE/AGR/UI0690/2014. The authors thank Serbian Ministry of Education, Science, and Technological Development for financial support (grant number 173032).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

References

  1. Abreu RMV, Ferreira ICFR, Calhelha RC, Lima RT, Vasconcelos MH, Adega F, Chaves R, Queiroz MJRP (2011) Anti-hepatocellular carcinoma activity using human HepG2 cells and hepatotoxicity of 6-substituted methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate derivatives: In vitro evaluation, cell cycle analysis and QSAR studies. Eur J Med Chem 46:5800–5806CrossRefPubMedGoogle Scholar
  2. Aguilar F, Charrondiere UR, Dusemund B, Galtier P, Gilbert J, Gott DM, Grilli S, Guertler R, Koenig J, Lambre C (2010) Scientific Opinion on the safety of sucrose esters of fatty acids prepared from vinyl esters of fatty acids and on the extension of use of sucrose esters of fatty acids in flavourings. EFSA J 8(3):1512–1548Google Scholar
  3. Avendaño C, Menéndez JC (2008) Medicinal chemistry of anticancer drugs. Elsevier, Amsterdam, OxfordGoogle Scholar
  4. Barros MT, Petrova KT (2009) Ziegler-Natta catalysed polymerisation for the preparation of copolymers with pendant sucrose moieties. Eur Polym J 45(1):295–301CrossRefGoogle Scholar
  5. Barros MT, Petrova KT, Correia-da-Silva P (2011) Sucrose chemistry: fast and efficient microwave-assisted protocols for the generation of sucrose-containing monomer libraries. In: Chandra U (ed) Microwave heating. InTech - Open Access Publisher, Rijeka, pp 309–332Google Scholar
  6. Barros MT, Petrova KT, Singh RP (2010) Synthesis of hydrophilic and amphiphilic acryl sucrose monomers and their copolymerisation with styrene, methylmethacrylate and α- and β-pinenes. Int J Mol Sci 11:1792–1807CrossRefPubMedPubMedCentralGoogle Scholar
  7. Butler MS, Cooper MA (2011) Antibiotics in the clinical pipeline in 2011. J Antibiot 64:413–425CrossRefPubMedGoogle Scholar
  8. Cardoso MM, Peça IN, Raposo CD, Petrova KT, Barros MT, Gardner R, Bicho A (2016) Doxorubicin-loaded galactoseconjugated poly(d,l-lactide-co-glycolide) nanoparticles as hepatocyte-targeting drug carrier. J Microencapsul 33(4):315–322CrossRefGoogle Scholar
  9. Carneiro MJ, Fernandes A, Figueiredo CM, Fortes AG, Freitas AM (2001) Synthesis of carbohydrate based polymers. Carbohydr Polym 45:135–138CrossRefGoogle Scholar
  10. Chortyk OT, Pomonis JP, Johnson AW (1996) Syntheses and characterizations of insecticidal sucrose esters. J Agric Food Chem 44:1551–1557CrossRefGoogle Scholar
  11. Clinical and Laboratory Standards Institute (2009) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard, 8th edn. CLSI publication M07-A8. Clinical and Laboratory Standards Institute, Wayne, PAGoogle Scholar
  12. Crucho CC, Correia-da-Silva P, Petrova KT, Barros MT (2015) Recent progress in the field of glycoconjugates. Carbohydr Res 402:124–132CrossRefPubMedGoogle Scholar
  13. Crucho CC, Petrova KT, Pinto RC, Barros MT (2008) Novel unsaturated sucrose ethers and their application as monomers. Molecules 13:762–770CrossRefGoogle Scholar
  14. Duynstee HI, Ovaa H, Marel GA, Boom JH (1996) Synthesis of niruriside a HIV REV/RRE binding inhibitor. Recl Trav Chim Pays-Bas 115:339–340CrossRefGoogle Scholar
  15. Dwek AR (1996) Glycobiology: toward understanding the function of sugars. Chem Rev 96(2):683–720CrossRefPubMedGoogle Scholar
  16. Espinel-Ingroff A (2001) Comparison of the E-test with the NCCLS M38-P method for antifungal susceptibility testing of common and emerging pathogenic filamentous fungi. J Clin Microbiol 39(4):1360–1367CrossRefPubMedPubMedCentralGoogle Scholar
  17. Fanton E, Fayet C, Gelas J, Jhurry D, Deffieux A, Fontanille M (1992) Ethylenic acetals of sucrose and their copolymerization with vinyl monomers. Carbohydr Res 226:337–343CrossRefGoogle Scholar
  18. Ferreira L, Vidal MM, Geraldes CF, Gil MH (2000) Preparation and characterisation of gels based on sucrose modified with glycidyl methacrylate. Carbohydr Polym 41:15–24CrossRefGoogle Scholar
  19. He R, Chen YF, Chen YH, Ougolkov AV, Zhang JS, Savoy DN, Billadeau DD, Kozikowski AP (2010) Synthesis and biological evaluation of triazol-4-ylphenyl-bearing histone deacetylase inhibitors as anticancer agents. J Med Chem 53(3):1347–1356CrossRefPubMedPubMedCentralGoogle Scholar
  20. Iwami Y, Schachtele CF, Yamada T (1995) Effect of sucrose monolaurate on acid production, levels of glycolytic intermediates, and enzyme activities of Streptococcus mutans NCTC 10449. J Dent Res 74(9):1613–1617CrossRefPubMedGoogle Scholar
  21. Jhurry D, Deffieux A, Fontanille M (1992) Sucrose based polymers. Linear polymers with sucrose side-chains. Makromol Chem 193:2997–3007CrossRefGoogle Scholar
  22. Kitaoka M, Imamura K, Hirakawa Y, Tahara Y, Kamiya N, Goto M (2014) Sucrose laurate-enhanced transcutaneous immunization with a solid-in-oil nanodispersion. MedChemComm 5:20–24CrossRefGoogle Scholar
  23. Klein J, Kunz M, Kowalczyk J (1990) Poly(vinylsaccharide)s, 7 New surfactant polymers based on carbohydrates. J Makromol Chem 191(3):517–528CrossRefGoogle Scholar
  24. Kobayashi K, Sumitomo H, Ina Y (1985) Synthesis and functions of polystyrene derivatives having pendant oligosaccharides. Polym J 17:567–575CrossRefGoogle Scholar
  25. Lichtenthaler FW, Peters S (2004) Carbohydrates as green raw materials for the chemical industry. C R Chim 7:65–90CrossRefGoogle Scholar
  26. Liu J, Head E, Kuratsune H, Cotman CW, Ames BN (2004) Comparison of the Effects of L-Carnitine and Acetyl-L-carnitine on carnitine levels, ambulatory activity, and oxidative stress biomarkers in the brain of old rats. Ann N Y Acad Sci 1033:117–131CrossRefPubMedGoogle Scholar
  27. Marshall DL, Bullerman LB (1986) Antimicrobial activity of sucrose fatty acid ester emulsifiers. J Food Sci 51(2):468–470CrossRefGoogle Scholar
  28. Neal JJ, Tingey WM, Steffens JC (1990) Sucrose esters of carboxylic acids in glandular trichomes of Solanum berthaultii deter settling and probing by green peach aphid. J Chem Ecol 16(2):487–497CrossRefPubMedGoogle Scholar
  29. Panda P, Appalashetti M, Judeh ZMA (2011) Phenylpropanoid sucrose esters: plant-derived natural products as potential leads for new therapeutics. Curr Med Chem 18:3234–3251CrossRefPubMedGoogle Scholar
  30. Panda P, Appalashetti M, Natarajan M, Chan-Park MB, Venkatraman SS, Judeh ZMA (2012a) Synthesis and antitumor activity of lapathoside D and its analogs. Eur J Med Chem 53:1–12CrossRefPubMedGoogle Scholar
  31. Panda P, Appalashetti M, Natarajan M, Mary CP, Venkatraman SS, Judeh ZMA (2012b) Synthesis and antiproliferative activity of helonioside A, 3,4,6-tri-O-feruloylsucrose, lapathoside C and their analogs. Eur J Med Chem 58:418–430CrossRefPubMedGoogle Scholar
  32. Patil DR, Dordick JS, Retwisch D (1991) Chemoenzymatic synthesis of novel sucrose-containing polymers. Macromolecules 24:3462–3463CrossRefGoogle Scholar
  33. Peça IN, Petrova KT, Cardoso MM, Barros MT (2012) Preparation and characterization of polymeric nanoparticles composed of poly(DL-lactide-co-glycolide) and poly(DL-lactide-co-glycolide)-co-poly(ethylene glycol) 10%Triblock end-capped with a galactose moiety. React Funct Polym 72(10):729–735CrossRefGoogle Scholar
  34. Petrova KT, Correia-da-Silva P, Crucho CC, Barros MT (2014a) Chemoselective synthesis of sucrose building blocks and their polymerization. Curr Org Chem 18(13):1788–1802CrossRefGoogle Scholar
  35. Petrova KT, Dey SS, Barros MT (2015a) Formation of spherical and core-shell polymeric microparticles from glycopolymers. Carbohydr Polym 125:281–287CrossRefPubMedGoogle Scholar
  36. Petrova KT, Potewar TM, Ascenso OS, Barros MT (2014b) Amide-linked N-methacryloyl sucrose containing polymers. Carbohydr Polym 110:38–46CrossRefPubMedGoogle Scholar
  37. Petrova KT, Potewar TM, Correia-da-Silva P, Barros MT, Calhelha RC, Ciric A, Sokovic M, Ferreira ICFR (2015b) Antimicrobial and cytotoxic activities of 1,2,3-triazole-sucrose derivatives. Carbohydr Res 417:66–71CrossRefPubMedGoogle Scholar
  38. Potewar TM, Petrova KT, Barros MT (2013) Efficient microwave assisted synthesis of novel 1,2,3-triazole-sucrose derivatives by cycloaddition reaction of sucrose azides and terminal alkynes. Carbohydr Res 379:60–67CrossRefPubMedGoogle Scholar
  39. Qian-Cutrone J, Huang S, Trimble J, Li H, Lin PF, Alam M, Klohr SE, Kadow KF (1996) Niruriside, a new HIV REV/RRE binding inhibitor from Phyllanthus niruri. J Nat Prod 59:196–199CrossRefPubMedGoogle Scholar
  40. Queneau Y, Jarosz S, Lewandowski B, Fitremann J (2008) Sucrose chemistry and applications of sucrochemicals. Adv Carbohydr Chem Biochem 61:217–292CrossRefGoogle Scholar
  41. Raposo CD, Petrova KT, Barros MT (2014) Microwave-assisted protocols applied to the synthesis of 1′,2,3,3′,4,4′-hexa-O-benzylsucrose. Synth Commun 44(20):3027–3036CrossRefGoogle Scholar
  42. Raposo CD, Petrova KT, Barros MT (2015) Synthesis of cross-linked polymeric microparticles containing hexa-O-benzylsucrose. Des Monomers Polym 18(8):753–760CrossRefGoogle Scholar
  43. Raposo CD, Petrova KT, Barros MT, Calhelha RC, Sokovic M, Ferreira ICFR (2016) Synthesis, characterization, antimicrobial and antitumor activities of sucrose octa(N-ethyl)carbamate. Med Chem 12(1):22–29CrossRefPubMedGoogle Scholar
  44. Shen Y, Sun Y, Sang Z, Sun C, Dai Y, Deng Y (2012) Synthesis, characterization, antibacterial and antifungal evaluation of novel monosaccharide esters. Molecules 17:8661–8673CrossRefPubMedGoogle Scholar
  45. Tsukatani T, Suenaga H, Shiga M, Noguchi K, Ishiyama M, Ezoe T, Matsumoto K (2012) Comparison of the WST-8 colorimetric method and the CLSI broth microdilution method for susceptibility testing against drug-resistant bacteria. J Microbiol Methods 90(3):160–166CrossRefPubMedGoogle Scholar
  46. Varma AJ, Kennedy JF, Galgali P (2004) Synthetic polymers functionalized by carbohydrates: a review. Carbohydr Polym 56:429–445CrossRefGoogle Scholar
  47. Xin L (2014) Antimicrobial structure-efficacy relationship of sugar fatty acid esters. J Chem Pharm Res 6(5):944–946Google Scholar
  48. Xu JP (2016) Cancer inhibitors from Chinese natural medicines. CRC Press, Taylor & Francis GroupGoogle Scholar
  49. Yang CM, Luedecke LO, Swanson BG, Davidson PM (2003) Inhibition of microorganisms in salad dressing by sucrose and methylglucose fatty acid aminoesters. J Food Process Preserv 27(4):285–298CrossRefGoogle Scholar
  50. Ye R, Hayes DG, Burton R, Liu A, Harte FM, Wang Y (2016) Solvent-free lipase-catalyzed synthesis of technical-grade sugar esters and evaluation of their physicochemical and bioactive properties. Catalysts 6(78):1–13Google Scholar
  51. Zhang CR, Khan W, Bakht J, Nair MG (2015) New antiinflammatory sucrose esters in the natural sticky coating of tomatillo (Physalis philadelphica), an important culinary fruit. Food Chem 196:726–732CrossRefPubMedGoogle Scholar
  52. Zhao L, Zhang H, Hao T, Li S (2015) In vitro antibacterial activities and mechanism of sugar fatty acid esters against five food-related bacteria. Food Chem 187:370–377CrossRefPubMedGoogle Scholar
  53. Ziemska J, Rajnisz A, Solecka J (2013) New perspectives on antibacterial drug research. Cent Eur J Biol 8(10):943–957Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.LAQV, REQUIMTE, Departamento de QuímicaFaculdade de Ciências e Tecnologia, Universidade Nova de LisboaCaparicaPortugal
  2. 2.Mountain Research Centre (CIMO), ESAPolytechnic Institute of BragançaBragançaPortugal
  3. 3.Department of Plant PhysiologyUniversity of Belgrade, Institute for Biological Research, “Siniša Stanković”BelgradeSerbia

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