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“1,3-di(thiophen-2-yl) prop-2-en-1-one” kalkon türevinin antifungal, anti-biyofilm ve anti-kanser aktivitelerinin belirlenmesi

Year 2017, Volume: 39 Issue: 2, 466 - 472, 17.05.2017

Uğur Tutar , Cem Çelik , Hayreddin Gezegen , Ceylan Hepokur

https://doi.org/10.7197/223.v39i29491.316366

Abstract

Amaç: Çalışmamızın amacı, literatürde rapor
edilen beş kalkon bileşiğinin Candida albicans
ve Candida tropicalis’e karşı
potansiyel antifungal ve antibiyofilm
aktivitelerinin belirlenmesidir. Ayrıca antimikrobiyal aktivitesi belirlenen
“1,3-di(thiophen-2-yl)prop-2-en-1-one” kalkon bileşiğinin antioksidan ve insan
meme kanseri (MCF-7) ve kemik kanseri (MG63) hücre hatları üzerindeki
etkilerinin belirlenmesi amaçlanmıştır.

Yöntem:
Çalışmada kullanılan kalkonlar dimeti
sülfoksit (DMSO) içinde iki kat seyreltilmiş ve 1000-15 μg/mL  konsantrasyonda hazırlanmıştır. Kalkonların
antifungal ve anti-biyofilm aktiviteleri mikrodilüsyon yöntemi kullanılarak
belirlenmiştir. Radikal süpürücü etkisi 2, 2-diphenyl-1-picrylhydrazyl (DPPH)
ile test edilmiştir. Hücre canlılığı , kültür ortamına ilave edilen tetrazolium
tuzları ile değerlendirilmiştir.

Bulgular:
Çalışmamızda antimikrobiyal aktivite
gösteren “1,3-di (tiyofen-2-il) prop-2-en-1-on” C. albicans ve C. tropicalis
üzerinde MIC değerleri 0.06 mg/mL bulunmuştur. MBC değerleri ise sırasıyla 0.12
mg/mL ve 0.5 mg/mL olarak saptanmıştır. MBIC aktiviteleri ise sırasıyla 0.06 ve
0.25 mg/mL olarak bulunmuştur. MBEC değerleri her iki mikroorganizma için 1
mg/mL bulunmuştur. C. albicans ve C. tropicalis’ in 48 saatlik biyofilm
yapılarına MIC değeri uygulandığında yapının sırasıyla 83% ve 81% oranında
azaldığı saptanmıştır. “1,3-di(thiophen-2-yl) prop-2-en-1-one” IC50 değeri
13,52 µg/L olarak bulundu. MCF-7 ve MG63 hücre hatlarında 5 µg/mL
konsantrasyonda 24 saat inkübasyon sonrasında sırasıyla hücrelerin  % 30’u ve 
% 65’ i  canlı kalmıştır.  







Sonuç:
Elde edilen sonuçlara göre tiyofen
halkası içeren kalkon bileşiği C.
albicans ve C. tropicalis  suşları üzerinde hem üremelerini inhibe edici
etki göstermiş hem de gerek biyofilm oluşumunda gerekse oluşan biofilm üzerinde
etkili olduğu görülmüştür. Çalışmanın sonuçları tiyofen halkası içeren kalkon
bileşiğinin potansiyel antimikrobiyal, antibiyofilm ve antikanser ajan olarak
değerli olabileceğini ortaya koymuştur.

Keywords

Kalkon antifungal anti-biyofilm anti-kanser

References

  • 1. Chandra J, Mukherjee PK. Candida Biofilms: Development, Architecture, and Resistance. Microbiol Spectr 2015; 3: doi: 10.1128/microbiolspec.MB-0020-2015.
  • 2. Faria S, Joao I, Jordao J. General overview on nontuberculous mycobacteria, biofilms, and human infection. J Pathog 2015; 2015: 809014.
  • 3. Akbari F, Kjellerup BV. Elimination of bloodstream infections associated with Candida albicans biofilm in intravascular catheters. Pathogens 2015; 4: 457-69.
  • 4. Tutar U, Çelik C, Ataş M, Tunç T, Gözel MG. Evaluation of biofilm formation activity of standard microorganism strains. J Clin Exp Invest 2015; 6: 135-9.
  • 5. Prabodh, CS, Sunil VS, Sandeep J, Dalbir S, Bhojraj S. Synthesis of some new isoxazoline derivatives as possible anti-candida agents. Acta Pol Pharm Drug Res 2009; 66: 101-12.
  • 6. El-Hashash MA, Rizk SA, Atta-Allah SR. Synthesis and regioselective reaction of some unsymmetrical heterocyclic chalcone derivatives and spiro heterocyclic compounds as antibacterial agents. Molecules 2015; 20: 22069-83.
  • 7. Mukherjee S, Kumar V, Prasad AK, Raj HG, Bracke ME, Olsen CE, Jain SC, Parmar VS. Synthetic and biological activity evaluation studies on novel 1,3-diarylpropenones. Bioorg Med Chem 2001; 9: 337-45.
  • 8. Anto RJ, Sukumaran K, Kuttan G, Rao MN, Subbaraju V, Kuttan R. Anticancer and antioxidant activity of synthetic chalcones and related compounds. Cancer Lett 1995; 97: 33-7.
  • 9. Ram VJ, Saxena AS, Srivastava S, Chandra S. Oxygenated chalcones and bischalcones as potential antimalarial agents. Bioorg Med Chem Lett 2000; 10: 2159-61.
  • 10. Vogel S, Barbic M, Jurgenliemk G, Heilmann J. Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect. European Journal of Medicinal Chemistry 2010; 45: 2206-13.
  • 11. Tran TD, Nguyen TTN, Do TH, Huynh TNP, Tran CD, Thai KM. Synthesis and antibacterial activity of some heterocyclic chalcone analogues alone and in combination with antibiotics. Molecules 2012; 17: 6684-96.
  • 12. de Vasconcelos A, Campos VF, Nedel F, Seixas FK, Dellagostin OA, Smith KR. Cytotoxic and apoptotic effects of chalcone derivatives of 2-acetyl thiophene on human colon adenocarcinoma cells. Cell Biochem Funct 2013; 31: 289-97.
  • 13. Rizvi SUF, Siddiqui HL, Nisar M, Khan N, Khan I. Discovery and molecular docking of quinolyl-thienyl chalcones as anti-angiogenic agents targeting VEGFR-2 tyrosine kinase. Bioorg Med Chem Lett 2012; 22: 942-4.
  • 14. Hwang KJ, Kim HS, Han IC, Kim BT. Synthesis of heterocyclic chalcone derivatives and their radical scavenging ability toward 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) free radicals. Bull Korean Chem Soc 2012; 33: 2585.
  • 15. Basavaiah D, Reddy RM. One-pot inter- and intramolecular Friedel–Crafts reactions in Baylis–Hillman chemistry: a novel facile synthesis of (E)-2-arylideneindan-1-ones. Tet Lett 2001; 42: 3025-7.
  • 16. Wattanasin S, Murphy WS. An improved procedure for the preparation of chalcones and related enones, Synthesis 1980; 647-50.
  • 17. Clinical and Laboratory Standards Institute (CLSI) M27-A3. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard- third edition. 2008.
  • 18. Adukwu EC, Allen SC, Phillips CA. The anti-biofilm activity of lemongrass (Cymbopogon flexuosus) and grapefruit (Citrus paradisi) essential oils against five strains of Staphylococcus aureus. J Appl Microbiol 2012; 113: 1217-27.
  • 19. Kuzma L, Rozalski M, Walencka E, Rozalska B, Wysokinska H. Antimicrobial activity of diterpenoids from hairy roots of Saliva sclarea L: salvipisone as a potential anti-biofilm agent active against antibiotic resistant Staphylococci. Phytomedicine 2007; 14: 31-5.
  • 20. Kose M, Hepokur C, Karakas D, McKee V, Kurtoglu M. Structural, computational and cytotoxic studies of square planar copper (II) complexes derived from dicyandiamide. Polyhedron 2016; 117: 652-60.
  • 21. Ou B, Huang, D, Hampsch-Woodill, M, Flanagan, JA, Deemer, EK. Analysis of antioxidant activities of common vegetables employing oxygen radical absorbance capacity (orac) and ferric reducing antioxidant power (frap) assays: a comparative study. J Agric Food Chem 2002; 50: 3122-8.
  • 22. Asiri AM, Khan SA. Synthesis and anti-bacterial activities of a bis-chalcone derived from thiophene and its bis-cyclized products. Molecules 2011; 16: 523-31.
  • 23. Kheder NA, Mabkhot YN. Synthesis and antimicrobial studies of some novel bis-[1, 3, 4] thiadiazole and bis-thiazole pendantto thieno [2, 3-b] thiophene moiety. Int J Mol Sci 2012; 13: 3661-70.
  • 24. Taff HT, Mitchell KF, Edward JA, Andes DR. Mechanisms of Candida biofilm drug resistance. Future Microbiol. 2013; 8: 1325-37.

Determining antifungal, anti-biofilm and anticancer activities of “1,3-di(thiophen-2-yl) prop-2- en-1-one” chalcone derivative

Year 2017, Volume: 39 Issue: 2, 466 - 472, 17.05.2017

Uğur Tutar , Cem Çelik , Hayreddin Gezegen , Ceylan Hepokur

https://doi.org/10.7197/223.v39i29491.316366

Abstract

Objective: Our study aims to determine
antifungal and anti-biofilm activity potential of five chalcone derivatives,
which have been already reported in the literature, against Candida albicans and Candida tropicalis.  In addition, it aimed to determine
antioxidant property and anti-cancer activity of
1,3-di(thiophen-2-yl)prop-2-en-1-one chalcone derivative, whose antimicrobial
activity was revealed within the study, in human breast cancer cell line
(MCF-7) and human bone cancer cell line (MG63).

Method: Chalcones used in the study
were diluted two times in dimethyl sulfoxide (DMSO) and prepared at
concentration between 1000-15 µg/mL. Antifungal and anti-biofilm activity of
chalcones determined by using microdilution method. Radical
scavenging activity was tested by employing 2, 2-diphenyl-1-picrylhydrazyl
(DPPH). The cell viability was
assessed using the cleavage of tetrazolium salts added to the culture medium.

Results: In our study, MIC values of “1,3-di(thiophen-2-yl) prop-2-en-1-one”, which showed
its antimicrobial activity on C. albicans
and C. tropicalis, were found to be
0.06 mg/mL for both organisms, whereas its MBC values were found to be 0.12
mg/mL and 0.50 mg/mL respectively. MBIC activities were found to be 0.06 and
0.25 mg/mL respectively, whereas MBEC values were found to be 1 mg/mL. When MIC
was applied to 48-hours biofilm formation,
it was observed that the formation has decreased by 83% and 81%.  IC50 value of
“1,3-di(thiophen-2-yl) prop-2-en-1-one” was found to be 13,52 µg / mL.
Regarding MCF-7 and MG63 cell line at 5 µg / mL concentration, 30% and 65%
preserve its viability after 24 hours of incubation respectively.







Conclusions: According to these results, it can be said that chalcone compound that
include thiophen ring has shown an inhibiting effect on the multiplication and
both on the formation of the biofilm of C.
albicans and C. tropicalis strains.
The results of the study revealed that chalcone compound may be valuable as an
antifungal, anti-biofilm and anti-cancer agent.  

Keywords

Chalcone antifungal anti-biofilm anti-cancer

References

  • 1. Chandra J, Mukherjee PK. Candida Biofilms: Development, Architecture, and Resistance. Microbiol Spectr 2015; 3: doi: 10.1128/microbiolspec.MB-0020-2015.
  • 2. Faria S, Joao I, Jordao J. General overview on nontuberculous mycobacteria, biofilms, and human infection. J Pathog 2015; 2015: 809014.
  • 3. Akbari F, Kjellerup BV. Elimination of bloodstream infections associated with Candida albicans biofilm in intravascular catheters. Pathogens 2015; 4: 457-69.
  • 4. Tutar U, Çelik C, Ataş M, Tunç T, Gözel MG. Evaluation of biofilm formation activity of standard microorganism strains. J Clin Exp Invest 2015; 6: 135-9.
  • 5. Prabodh, CS, Sunil VS, Sandeep J, Dalbir S, Bhojraj S. Synthesis of some new isoxazoline derivatives as possible anti-candida agents. Acta Pol Pharm Drug Res 2009; 66: 101-12.
  • 6. El-Hashash MA, Rizk SA, Atta-Allah SR. Synthesis and regioselective reaction of some unsymmetrical heterocyclic chalcone derivatives and spiro heterocyclic compounds as antibacterial agents. Molecules 2015; 20: 22069-83.
  • 7. Mukherjee S, Kumar V, Prasad AK, Raj HG, Bracke ME, Olsen CE, Jain SC, Parmar VS. Synthetic and biological activity evaluation studies on novel 1,3-diarylpropenones. Bioorg Med Chem 2001; 9: 337-45.
  • 8. Anto RJ, Sukumaran K, Kuttan G, Rao MN, Subbaraju V, Kuttan R. Anticancer and antioxidant activity of synthetic chalcones and related compounds. Cancer Lett 1995; 97: 33-7.
  • 9. Ram VJ, Saxena AS, Srivastava S, Chandra S. Oxygenated chalcones and bischalcones as potential antimalarial agents. Bioorg Med Chem Lett 2000; 10: 2159-61.
  • 10. Vogel S, Barbic M, Jurgenliemk G, Heilmann J. Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect. European Journal of Medicinal Chemistry 2010; 45: 2206-13.
  • 11. Tran TD, Nguyen TTN, Do TH, Huynh TNP, Tran CD, Thai KM. Synthesis and antibacterial activity of some heterocyclic chalcone analogues alone and in combination with antibiotics. Molecules 2012; 17: 6684-96.
  • 12. de Vasconcelos A, Campos VF, Nedel F, Seixas FK, Dellagostin OA, Smith KR. Cytotoxic and apoptotic effects of chalcone derivatives of 2-acetyl thiophene on human colon adenocarcinoma cells. Cell Biochem Funct 2013; 31: 289-97.
  • 13. Rizvi SUF, Siddiqui HL, Nisar M, Khan N, Khan I. Discovery and molecular docking of quinolyl-thienyl chalcones as anti-angiogenic agents targeting VEGFR-2 tyrosine kinase. Bioorg Med Chem Lett 2012; 22: 942-4.
  • 14. Hwang KJ, Kim HS, Han IC, Kim BT. Synthesis of heterocyclic chalcone derivatives and their radical scavenging ability toward 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) free radicals. Bull Korean Chem Soc 2012; 33: 2585.
  • 15. Basavaiah D, Reddy RM. One-pot inter- and intramolecular Friedel–Crafts reactions in Baylis–Hillman chemistry: a novel facile synthesis of (E)-2-arylideneindan-1-ones. Tet Lett 2001; 42: 3025-7.
  • 16. Wattanasin S, Murphy WS. An improved procedure for the preparation of chalcones and related enones, Synthesis 1980; 647-50.
  • 17. Clinical and Laboratory Standards Institute (CLSI) M27-A3. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard- third edition. 2008.
  • 18. Adukwu EC, Allen SC, Phillips CA. The anti-biofilm activity of lemongrass (Cymbopogon flexuosus) and grapefruit (Citrus paradisi) essential oils against five strains of Staphylococcus aureus. J Appl Microbiol 2012; 113: 1217-27.
  • 19. Kuzma L, Rozalski M, Walencka E, Rozalska B, Wysokinska H. Antimicrobial activity of diterpenoids from hairy roots of Saliva sclarea L: salvipisone as a potential anti-biofilm agent active against antibiotic resistant Staphylococci. Phytomedicine 2007; 14: 31-5.
  • 20. Kose M, Hepokur C, Karakas D, McKee V, Kurtoglu M. Structural, computational and cytotoxic studies of square planar copper (II) complexes derived from dicyandiamide. Polyhedron 2016; 117: 652-60.
  • 21. Ou B, Huang, D, Hampsch-Woodill, M, Flanagan, JA, Deemer, EK. Analysis of antioxidant activities of common vegetables employing oxygen radical absorbance capacity (orac) and ferric reducing antioxidant power (frap) assays: a comparative study. J Agric Food Chem 2002; 50: 3122-8.
  • 22. Asiri AM, Khan SA. Synthesis and anti-bacterial activities of a bis-chalcone derived from thiophene and its bis-cyclized products. Molecules 2011; 16: 523-31.
  • 23. Kheder NA, Mabkhot YN. Synthesis and antimicrobial studies of some novel bis-[1, 3, 4] thiadiazole and bis-thiazole pendantto thieno [2, 3-b] thiophene moiety. Int J Mol Sci 2012; 13: 3661-70.
  • 24. Taff HT, Mitchell KF, Edward JA, Andes DR. Mechanisms of Candida biofilm drug resistance. Future Microbiol. 2013; 8: 1325-37.
There are 24 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Basic Science Research Articles
Authors

Uğur Tutar

Cem Çelik

Hayreddin Gezegen

Ceylan Hepokur

Publication Date May 17, 2017
Acceptance Date March 21, 2017
Published in Issue Year 2017 Volume: 39 Issue: 2

Cite

AMA Tutar U, Çelik C, Gezegen H, Hepokur C. Determining antifungal, anti-biofilm and anticancer activities of “1,3-di(thiophen-2-yl) prop-2- en-1-one” chalcone derivative. CMJ. May 2017;39(2):466-472. doi:10.7197/223.v39i29491.316366