Yıl: 2013 Cilt: 10 Sayı: 2 Sayfa Aralığı: 193 - 204 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation

Öz:
Ruthenium (II) komplekslerinin DNA bağlanması He ilgili olan yüksek antitumor aktiviteleri nedeni He bu bileşikler son yıllarda araştırmacıların yoğun ilgisini çekmektedir. Bu çalismada imidazo[4,5-f][ 1,10]fenantrolin (ip) and 2-fenilimidazo[4,5-f][ 1,10]fenantrolin (pip) ligand olarak kullanılarak, iki rutenyum (II) kompleksi sentezlenmiş olup, bu bileşikler spektroskobik ve elemental analiz yöntemleri He karakterize edilmiştir. İlk olarak, bu komplekslerin insan akciğer karsinoma, A549 hücreleri üzerine olan ölümcül etkileri araştırHmıştır. MTT deneyi He elde edilen sitotoksik sonuçlar göstermiştir ki, A 549 hücrelerinin 24 saat imidazo[4,5-f][1,10]fenantrolin Ru(II) kompleksi [Ru(ip)3](PF6)2 ve 2-fenilimidazo[4,5-f][ 1,10]fenantrolin Ru(II) kompleksi [Ru(pip)3](PF6)2 ile inkübasyonu sonucunda IC50 değerlerinin sırasıyla yaklasik olarak 32 ve 46 jug/mldır.ilginçtir ki, bu komplekler normal insan akciğer hücrelerine karsi dusuk sitotoksik etkiye sahiptirler (IC50 > 80 ug/ml).BrdU bağlanma deneyi sonucunda, [Ru(pip)3](PF6)2 kompleksinin diğer hücrelere kıyasla A549 hücreleri üzerinde güçlü baskılayıcı etkiye sahip olduğu gdrülmustiir. [Ru(pip)3](PF6)2 kompleksinin dana timus DNA sı He etkileşimi sonrasında DNA baglanma aktivitesinin arttigi viskozite deneyi He tespit edilmiştir.Özet olarak, [Ru(pip)3](PF6)2 kompleksi anlamh sitoksik etki ve A549 hiicre çoğalması üzerine inhibitor bir etki göstermiştir. Bu kompleksin güçlü tedavi edici bir etkiye sahip olabileceği ve bu nedenle tedavi edici ajanların geliştirilmesi için farklı in vitro biyoassaylar kullanarak araştırılması gerekliliği varsayılmaktadır.
Anahtar Kelime:

Konular: Farmakoloji ve Eczacılık

Bazı fenantrolin rutenyum (II) komplekslerinin A549 hücre çoğalması üzerine etkileri

Öz:
In recent years, ruthenium (II) complexes have increasingly attracted the interest of researchers because of their high antitumor activities that are usually related to DNA binding. Here, we synthesized two ruthenium (II) complexes, using imidazo[4,5-f][1,10]phenanthroline (ip) and 2-phenylimidazo[4,5-f][1,10]phenanthroline (pip) that were characterized by spectroscopic and elemental analyses. First of all, we investigated the ability of these complexes to produce lethal effects in human lung carcinoma, A 549 cells. The cytotoxicity results evaluated by the MTT assay, revealed that the IC50for Ru(II) complexes of imidazo[4,5-f][1,10]phenanthroline [Ru(ip)3](PF6)2 and 2-phenylimidazo[4,5-f][1,10]phenanthroline [Ru(pip)3](PF6)2 after 24 h of incubation with A549 cells was approximately 32 and 46 jilg/ml, respectively. Interestingly, it was observed that these complexes showed weak cytotoxic effects in normal human lung cells (IC50 > 80 ug/ml). [Ru(pip)3](PF6)2 has a potent inhibitory effects on A549 compared to other cells as measured by BrdU labeling assay. Treatment of DNA with [Ru(pip)3](PF6)2induced DNA binding activity, which was demonstrated by a viscosity assay. In summary, Ru(II) complexes of [Ru(pip)3](PF6)2 showed significant cytotoxic and anti-proliferative effects on A549 cells, suggesting that this complex may have potential therapeutic agent, and therefore, this must be further investigated by other in vitro bioassays for the development of therapeutic agents.
Anahtar Kelime:

Konular: Farmakoloji ve Eczacılık
Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Metcalf C, Thomas JA, Kinetically inert transition metal complexes that reversibly bind to DNA, Chem Soc Rev 32, 215-224, 2003.
  • 2. Blasius R, Moucheron C, Kirsch-De Mesmaeker A, Photo adducts of metallic compounds with nucleic acids - Role played by the photoelectron transfer process and by the TAP and HAT ligands in the Ru (II) complexes, Eur J Inorg Chem 20, 3971-3979, 2004.
  • 3. Chao H, Mei WJ, Huang QW, Ji LN, DNA binding studies of ruthenium (II) complexes containing asymmetric tridentate ligands, J Inorg Biochem 92,165-170, 2002.
  • 4. Patel KK, Plummer EA, Darwish M, Rodger A, Hannon MJ, Aryl substituted ruthenium bis-terpyridine complexes: intercalation and groove binding with DNA, J Inorg Biochem 91, 220-225, 2002.
  • 5. Lawrence D, Vaidyanathan VG, Nair BU, Synthesis, characterization and DNA binding studies of two mixed ligand complexes of ruthenium(II), J Inorg Biochem 100, 1244-1251, 2006.
  • 6. Jang YJ, Kwon BH, Choi B-H, Bae CH, Seo MS, Nam W, Kim SK, Intercalation of bulky Delta,Delta- and Lambda,Lambda-bis-Ru(II) complex between DNA base pairs, J Inorg Biochem 102, 1885-1891, 2008.
  • 7. Tan L-F, Liu X-H, Chao H, Ji L-N, Synthesis, DNA-binding and photocleavage studies of ruthenium(II) complex with 2-(3'-phenoxyphenyl)imidazo[4,5-f][1,10]phenanthroline, J Inorg Biochem 101, 56-63, 2007.
  • 8. Deng H, Li J, Zheng KC, Yang Y, Chao H, Ji LN, Synthesis, characterization structures and DNA-binding properties of complexes [Ru(bpy)2(L)]2+ (L = ptdb, ptda and ptdp) with asymmetric intercalative ligands, Inorg Chim Acta 358, 3430-3440, 2005.
  • 9. Zimmer CH, Wahnert U, Nonintercalating DNA-binding ligands: Specificity of the interaction and their use as tools in biophysical, biochemical and biological investigations of the genetic material, Prog Biophy Mol Biol 47, 31-112, 1986.
  • 10. Norden B, Lincoln P, Akerman B, Tuite E, Sigel A, Sigel H, Metal Ions in Biological Systems, pp 251-295, Marcel Dekker Press, New York, 1996.
  • 11. Ji L-N, ouX-HZ, Liu J-G, Shape- and enantioselective interaction of Ru(II)/Co(III) polypyridyl complexes with DNA, Coord Chem Rev 216, 513-517, 1997.
  • 12. Gao F, Chao H, Wang J-Q, Yuan Y-X, Sun B, Wei Y-F, Peng B.J, Targeting topoisomerase II with the chiral DNA-intercalating ruthenium(II) polypyridyl complexes, J Biol Inorg Chem 12, 1015-1027, 2007.
  • 13. Berger MR, Garzon FT, Keppler BK, Schmahl D, Efficacy of new ruthenium complexes against chemically induced autochthonous colorectal carcinoma in rats Anticancer Res 9, 761-766, 1989.
  • 14. Lecomte JP, Mesmaeker AKD, Demeunynck M, Lehomme J, Synthesis and characterization of a new DNA-binding bifunctional ruthenium (II) complex, J Chem Soc Faraday Trans 89:3261-3268, 1993.
  • 15. Mosmann TJ, Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays, Immunol Meth 65, 55-63, 1983.
  • 16. Chaires JB, Dattagupta N, Crothers DM, Self-association of daunomycin, Biochem 21, 3927-3932, 1982.
  • 17. Eisenberg H, Cohen G, An interpretation of the low-angle X-ray scattering of DNA solutions, J. Mol Biol 37, 355-360, 1968.
  • 18. Jiang C-W, Chao H, Li R-H, Li H, Ji L-N, Syntheses, characterization and third-order nonlinear optical properties of ruthenium(II) complexes containing 2-phenylimidazo-[4,5-f ][1,10]phenanthroline and extended dimine ligands, Polyhed 20, 2187-2192, 2001.
  • 19. Wu JZ, Ye BH, Wang L, Ji LN, Zhou JY, Li RH, Zhou ZY, Bis(2,2-bipyridine)ruthenium (II) complexes with imidazo[4,5-f][1,10]-phenanthroline or 2-phenylimidazo[4,5-f][1,19] phenanthroline, J Chem Soc Dalton Trans 119, 1395-1401, 1997.
  • 20. Jing B, Wu T, Zhang M, Shen T, pH-dependent luminescence of ruthenium (II) polypyridine complexes, Bull Chem Soc Jpn 73, 1749-1755, 2000.
  • 21. Novakova O, Kasparkova J, Vrana O, van Vliet PM, Reedijk J, Bradec V, Correlation between cytotoxicity and DNA-binding of polypyridyl ruthenium complexes, Biochem 34, 12369–12378, 1995.
  • 22. Grguric-Sipka SR, Vilaplana RA, Pérez JM, Fuertes MA, Alonso C, Alvarez Y, Sabo TJ, González-Vílchez F, Synthesis, characterization, interaction with DNA and cytotoxicity of the new potential antitumor drug cis-K[Ru(eddp)Cl2], J Inorg Biochem 97, 215–220, 2003.
  • 23. Sava G, Bergamo A, Drug control of solid tumour metastases: a critical view, Anticancer Res 19, 1117–1124, 1999.
  • 24. Liu Y-J, Zeng C-H, Yao J-H, Wu F-H, He L-X, Huang H-L, Synthesis, structure, DNA-binding properties, and cytotoxicity of ruthenium(II) polypyridyl complexes, Chem Biodivers 7, 1770-1783, 2010.
  • 25. Alessio E, Balducci G, Lutman A, Mestroni G, Calligaris H, Attia WM, Synthesis and characterization of two new classes of ruthenium (III)-sulfoxide complexes with nitrogen donor ligands (L): Na [trans-RuCl4 (R2SO) (L)] and mer, cis-RuCl3 (R2SO) (R2SO) (L). The crystal structure of Na [trans-RuCl4 (DMSO) (NH3)] · 2DMSO, Na [trans-RuCl4 (DMSO) (Im)] · H2O, Me2CO (Im = imidazole) and mer, cis-RuCl3 (DMSO) (DMSO) (NH3), Inorg Chim Acta 203, 205-217, 1993.
  • 26. Djinovic WM, Todorovic T, Zizak Z, Sabo TJ, Juranic AD, Ru(II) coplexes derived from N-methyl derivatives of glycine and 1, 3-propylenediamine-N, N’-diacetato ligands and their activities against HeLa, K562 cell lines and human PBMC, J Coord Chem 62, 328-336, 2009.
  • 27. Mulcahy SP, Gründler K, Frias C, Wagner L, Prokop A, Meggers E, Discovery of a strongly apoptotic ruthenium complexes through combinatorial coordination chemistry, Dalton Transd 39, 8177-8182, 2010.
  • 28. Kapitza S, Pangratz M, Jakupec MA, Heffeter P, Berger W, Lackinger L, Keppler BK, Marian B, Heterocyclic complexes of ruthenium(III) induce apoptosis in colorectal carcinoma cells, J Cancer Res Clin Oncol 131, 101-110, 2005.
  • 29. Garcia-Femandez A, Diez J, Manteca A, Sanchez J, Garcia-Navas R, Sierra BG, Mollinedo F, Gamasa MP, Lastra E, Antitumor activity of new hydridotris(pyrazolyl)borate ruthenium(II) complexes containing the phosphanes PTA and 1-CH3-PTA, Dalton Transact 39, 10186-10196, 2010.
  • 30. Frasca DR, Ciampa D, Emerson J, Umans RS, Clarke MJ, Effects of hypoxia and transferrin on toxicity and DNA binding of ruthenium antitumor agents in HeLa cells, Met-Based Drugs 3, 97-103, 1996.
  • 31. Linares F, Galindo MA, Galli S, Romero MA, Navarro JA, Barea E, Tetranuclear coordination assemblies based on half-sandwich ruthenium(II) complexes: noncovalent binding to DNA and cytotoxicity, Inorg Chem 48, 7413-7420, 2009.
  • 32. Marx KA, Kruger R, Clarke MJ, Binding of the transition metal ion [(H2O)(NH3)5Ru(II)]2+ to nucleosomal core and internucleosomal DNA, Mol Cell Biochem 86, 155-162, 1989.
  • 33. Zhang P, Chen J, Liang Y, DNA binding, cytotoxicity, and apoptotic-inducing activity of ruthenium (II) polypyridyl complex, Acta Biochim Biophys Shanghai 42, 440-449, 2010.
APA İNCESU Z, Benkli K, Akalın Çiftçi G, GÜNDOĞDU KARABURUN N (2013). The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation. , 193 - 204.
Chicago İNCESU Zerrin,Benkli Kadriye,Akalın Çiftçi Gülşen,GÜNDOĞDU KARABURUN NALAN The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation. (2013): 193 - 204.
MLA İNCESU Zerrin,Benkli Kadriye,Akalın Çiftçi Gülşen,GÜNDOĞDU KARABURUN NALAN The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation. , 2013, ss.193 - 204.
AMA İNCESU Z,Benkli K,Akalın Çiftçi G,GÜNDOĞDU KARABURUN N The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation. . 2013; 193 - 204.
Vancouver İNCESU Z,Benkli K,Akalın Çiftçi G,GÜNDOĞDU KARABURUN N The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation. . 2013; 193 - 204.
IEEE İNCESU Z,Benkli K,Akalın Çiftçi G,GÜNDOĞDU KARABURUN N "The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation." , ss.193 - 204, 2013.
ISNAD İNCESU, Zerrin vd. "The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation". (2013), 193-204.
APA İNCESU Z, Benkli K, Akalın Çiftçi G, GÜNDOĞDU KARABURUN N (2013). The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation. Turkish Journal of Pharmaceutical Sciences, 10(2), 193 - 204.
Chicago İNCESU Zerrin,Benkli Kadriye,Akalın Çiftçi Gülşen,GÜNDOĞDU KARABURUN NALAN The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation. Turkish Journal of Pharmaceutical Sciences 10, no.2 (2013): 193 - 204.
MLA İNCESU Zerrin,Benkli Kadriye,Akalın Çiftçi Gülşen,GÜNDOĞDU KARABURUN NALAN The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation. Turkish Journal of Pharmaceutical Sciences, vol.10, no.2, 2013, ss.193 - 204.
AMA İNCESU Z,Benkli K,Akalın Çiftçi G,GÜNDOĞDU KARABURUN N The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation. Turkish Journal of Pharmaceutical Sciences. 2013; 10(2): 193 - 204.
Vancouver İNCESU Z,Benkli K,Akalın Çiftçi G,GÜNDOĞDU KARABURUN N The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation. Turkish Journal of Pharmaceutical Sciences. 2013; 10(2): 193 - 204.
IEEE İNCESU Z,Benkli K,Akalın Çiftçi G,GÜNDOĞDU KARABURUN N "The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation." Turkish Journal of Pharmaceutical Sciences, 10, ss.193 - 204, 2013.
ISNAD İNCESU, Zerrin vd. "The effects of some phenanthroline ruthenium (II) complexes on a549 cell proliferation". Turkish Journal of Pharmaceutical Sciences 10/2 (2013), 193-204.