Yıl 2019, Cilt 8 , Sayı 2, Sayfalar 713 - 724 2019-06-28

Platin ve Bakır Temelli N-Heterosiklik Karben (NHC) Komplekslerinin Antikanser Özellikleri ve Etki Mekanizmaları

Aydın AKTAŞ [1]


Metal-N-Heterosiklik Karben (M-NHC) kompleksleri uzun yıllardır organometalik kimyada katalitik aktivite gösteren bileşikler olarak ön plana çıkmaktadırlar. Son yıllarda bu bileşiklerin biyolojik özelliklerini ön plana çıkaran çalışmalar yoğun ilgi görmektedir. Kanser çağımızın önemli bir hastalığı olup tedavisinde kullanılacak ilaçların keşfi oldukça önemlidir. Bu nedenle M-NHC komplekslerinin antikanser özellikleri ile ilgili çalışmalar önem kazanmıştır. Antikanser etki gösteren platin ve bakır temelli M-NHC kompleksleri, bu komplekslerin en önemli olanlarındandır. NHC’lere bağlı bulunan sübstitüentlerin değiştirilmesi ile M-NHC komplekslerinin antikanser aktiviteleride değişmektedir. Bu bileşiklerin antikanser etki mekanizmaları DNA mutasyonları ve Reaktif Oksijen Türleri (ROT)‘nden oluşur. Bununla beraber M-NHC komplekslerinin antikanser etki mekanizmalarını tam olarak ortaya koyacak ve yeni sentezlenecek komplekslere yol gösterecek çalışmalara ihtiyaç vardır.

N-heterosiklik karben, Metal-NHC kompleksleri, Antikanser ajan, DNA mutasyonu, Reaktif oksijen türleri
  • 1. Matzingerand S., Fulscher M.P. 1995. Methyl substitution in carbenes. A theoretica prediction of the singlet-triplet energy separation of dimethylcarbene. Journal of Physical Chemistry, 99 (27): 10747-10751.
  • 2. Öfele K. 1968. 1,3-Dimethyl-4-imidazolinyliden-(2)-pentacarbonylchrom ein neuer Übergangsmetall-carben-komplex. Journal Organometallic Chemistry, 12, 42-43.
  • 3. Wanzlick H.W., Schönherr H.J. 1968. Direct Synthesis of a Mercury Salt‐Carbene Complex. Angewandte Chemie International Edition, 7(2): 141-142.
  • 4. Sarı Y., Aktaş A., Barut Celepci D., Gök Y., Aygün M. 2017. Synthesis, Characterization and Crystal Structure of New 2-Morpholinoethyl-Substituted Bis-(NHC)Pd(II) Complexes and the Catalytic Activity in the Direct Arylation Reaction. Catalysis Letter, 147(9): 2340–2351.
  • 5. Gök Y., Aktaş A., Erdoğan H., Sarı Y. 2018. New 4-vinylbenzyl-substituted bis(NHC)-Pd(II) complexes: Synthesis, characterization and the catalytic activity in the direct arylation reaction. Inorganica Chimica Acta. 471: 735–740.
  • 6. Erdoğan H., Aktaş A., Gök Y., Sarı Y. 2018. N-Propylphthalimide-substituted bis-(NHC)PdX2 complexes: synthesis, characterization and catalytic activity in direct arylation reactions. Transition Metal Chemistry, 43(1): 31–37.
  • 7. Aktaş A., Akkoç S., Gök Y. 2013. Palladium catalyzed Mizoroki–Heck and Suzuki–Miyaura reactions using naphthalenomethyl-substituted imidazolidin-2-ylidene ligands in aqueous media. Journal of Coordination Chemistry, 66(16): 2901-2909.
  • 8. Haque R.A., Choo S.Y., Budagumpi S., Iqbal M.A., Abdullah A.A. 2015. Silver(I) complexes of mono- and bidentate N-heterocyclic carbene ligands: Synthesis, crystal structures, and in vitro antibacterial and anticancer studies. European Journal of Medicinal Chemistry, 90: 82-92.
  • 9. Li Y., Tan C.-P., Zhang W., He L., Ji L.-N., Mao Z.-W. 2015. Phosphorescent iridium(III)-bis-N-heterocyclic carbene complexes as mitochondria-targeted theranostic and photodynamic anticancer agents. Biomaterials 39: 95-104.
  • 10. Arduengo III A.J., Harlow R.L., Kline M. 1991. A Stable Crystalline Carbene. Journal of the American Chemical society,113(1): 361-363.
  • 11. Nguyen M.T., Nguyenand T.L., Le H.T. 1999. Theoretical Study of Dithioformic Acid, Dithiohydroxy Carbene and Their Radica Cations:  Unimolecularand Assisted Rearrangements. The Journal of Physical Chemistry A, 103(29): 5758-5765.
  • 12. Kühl O. 2010. Functionalised N-Heterocyclic Carbene Complexes. John Wiley&Sons, 7-8.
  • 13. Kühl O. 2009. Sterically induced differences in N-heterocyclic carbene transition metal complexes. Coordination Chemistry Reviews, 253(21-22): 2481-2492.
  • 14. Cisnetti F., Gautier A. 2013. Metal/N‐Heterocyclic Carbene Complexes: Opportunities for the Development of Anticancer Metallodrugs. Angewandte Chemie International Edition, 52(46): 11976- 11978.
  • 15. Aktaş A., Keleştemur Ü., Gök Y., Balcıoğlu S., Ateş B., Aygün M. 2017. Synthesis, characterization, crystal structure, and antimicrobial studies of 2-morpholinoethyl-substituted benzimidazolium salts and their silver(I)-N-heterocyclic carbene complexes. Research on Chemical Intermediates, 43(11): 6379–6393.
  • 16. Savić N.D., Glišić B.Đ., Wadepohl H., Pavic A., Senerovic L., Nikodinovic-Runic J., Djurana M.I. 2016. Silver(I) complexes with quinazoline and phthalazine: synthesis, structural characterization and evaluation of biological activities. Medicinal Chemistry Communication, 7: 282–291.
  • 17. Krishnamoorthy P., Sathyadevi P., Butorac R.R., Cowley A.H., Bhuvanesh N.S.P., Dharmaraj N. 2012. Copper(I) and nickel(II) complexes with 1[thin space (1/6-em)]:[thin space (1/6-em)]1 vs. 1[thin space (1/6-em)]:[thin space (1/6-em)]2 coordination of ferrocenyl hydrazone ligands: Do the geometry and composition of complexes affect DNA binding/cleavage, protein binding, antioxidant and cytotoxic activities? Dalton Transactions, 41:4423–4436.
  • 18. Li Y., Liu G.-F., Tan C.-P., Ji L.-N., Mao Z.-W. 2014. Antitumor properties and mechanisms of mitochondria-targeted Ag(I) and Au(I) complexes containing N-heterocyclic carbenes derived from cyclophanes. Metallomics, 6:1460-1468.
  • 19. Çetinkaya B., Özdemir İ., Binbaştoğlu B., Günal S. 1999. Antibacterial and Antifungal Activities of Complexes of Ruthenium (II). Arzneimitteforschung, 49(6): 538-540.
  • 20. Aktaş A., Taslimi P., Gülçin İ., Gök Y. 2017. Novel NHC Precursors: Synthesis, Characterization, and Carbonic Anhydrase and Acetylcholinesterase Inhibitory Properties. Archiv der Pharmazie, 350, DOI:10.1002/ardp.201700045.
  • 21. Sarı Y., Aktaş A., Taslimi P., Gök Y., Gülçin İ. 2017. Novel N‐propylphthalimide‐ and 4‐vinylbenzyl‐substituted benzimidazole salts: Synthesis, characterization, and determination of their metal chelating effects and inhibition profiles against acetylcholinesterase and carbonic anhydrase enzymes. Journal of Biochemical and Molecular Toxicology, doi.org/10.1002/jbt.22009.
  • 22. Erdemir F., Barut Celepci D., Aktaş A., Taslimi P., Gök Y., Karabıyık H., Gülçin İ. 2018. 2-Hydroxyethyl substituted NHC precursors: Synthesis, characterization, crystal structure and carbonic anhydrase, α-glycosidase, butyrylcholinesterase, and acetylcholinesterase inhibitory properties. Journal of Molecular Structure 1155: 797-806.
  • 23. Türker F., Barut Celepci D., Aktaş A., Taslimi P., Gök Y., Aygün M., Gülçin İ. 2018. meta‐Cyanobenzyl substituted benzimidazolium salts: Synthesis, characterization, crystal structure and carbonic anhydrase, α‐glycosidase, butyrylcholinesterase, and acetylcholinesterase inhibitory properties. Archiv der Pharmazie, doi.org/10.1002/ardp.201800029.
  • 24. Behçet A., Çağlılar T., Barut Celepci D., Aktaş A., Taslimi P., Gök Y., Aygün M., Kaya R., Gülçin İ. 2018. Synthesis, characterization and crystal structure of 2-(4-hydroxyphenyl)ethyl and 2-(4-nitrophenyl)ethyl Substituted Benzimidazole Bromide Salts: Their inhibitory properties against carbonic anhydrase and acetylcholinesterase. Journal of Molecular Structure, 1170: 160-169.
  • 25. Ott I., Gust R. 2007. Preclinical and Clinical Studies on the Use of Platinum Complexes for Breast Cancer Treatment. Anti-Cancer Agents in Medicinal Chemistry, 7(16): 95–110.
  • 26. Gust R., Beck W., Jaouen G, Schönenberger H, 2009. Optimization of cisplatin for the treatment of hormone-dependent tumoral diseases: Part 2: Use of non-steroidal ligands. Coordination Chemistry Reviews, 253(21-22): 2760–2779.
  • 27. Berners-Price S.J. 2011. Activating Platinum Anticancer Complexes with Visible Light. Angewandte Chemie International Edition, 50(4): 804–805.
  • 28. Wedlock L.E., Berners-Price S.J. 2011. Recent Advances in Mapping the Sub-cellular Distribution of Metal-Based Anticancer Drugs. Australian Journal of Chemistry, 64(6): 692–704.
  • 29. Wheate N.J., Walker S., Craig G.E., Oun R. 2010. The status of platinum anticancer drugs in the clinic and in clinical trials. Dalton Transactions, 39: 8113–8127.
  • 30. Monneret C. 2011. Platinum anticancer drugs. From serendipity to rational design. Annales Pharmaceutiques Françaises, 69(6): 286–295.
  • 31. Rabik C.A. Dolan ME. 2007. Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treatment Reviews, 33(1): 9-23.
  • 32. Gust R., Beck W., Jaouen G., Schönenberger H. 2009. Optimization of cisplatin for the treatment of hormone dependent tumoral diseases: Part 1: Use of steroidal ligands. Coordination Chemistry Reviews, 253(21-22): 2742–2759.
  • 33. Tan S.J. Yan Y.K., Lee P.P., Lim K.H. 2010. Copper, gold and silver compounds as potential new anti-tumor metallodrugs. Future Medicinal Chemistry, 2(10): 1591-1608.
  • 34. Scott L.E., Orvig C. 2009. Medicinal Inorganic Chemistry Approaches to Passivation and Removal of Aberrant Metal Ions in Disease. Chemical Reviewes, 109(10): 4885-4910.
  • 35. Hindi K.M., Panzner M.J., Tessier C.A., Cannon C.L., Youngs W.J. 2009. The Medicinal Applications of Imidazolium Carbene−Metal Complexes. Chem. Rev., 109(8): 3859-3884.
  • 36. Gautier A., Cisnetti F. 2012. Advances in metal–carbene complexes as potent anti-cancer agents. Metallomics, 4: 23-32.
  • 37. Mercs L., Albrecht M. 2010. Beyond catalysis: N-heterocyclic carbene complexes as components for medicinal, luminescent, and functional materials applications. Chemical Society Reviews, 39(6): 1903-1912.
  • 38. Liu W., Gust R. 2013. Metal N-heterocyclic carbene complexes as potential antitumor metallodrugs. Chemical Society Reviews, 42(2): 755-773.
  • 39. Alves G., Morel L., El-Ghozzi M., Avignant D., Legeret B., Nauton L., Cisnetti F., Gautier A. 2011. A platinum Chugaev carbene complex as a potent anticancer agent. Chemical Communications, 47(27): 7830–7832.
  • 40. Sun R.W.-Y., Chow A.L.-F., Li X.-H., Yan J.J., Chui S.S.-Y., Che C.-M. 2011. Luminescent cyclometalated platinum(II) complexes containing N-heterocyclic carbene ligands with potent in vitro and in vivo anti-cancer properties accumulate in cytoplasmic structures of cancer cells, Chemical Science, 2: 728-736.
  • 41. Trachootham D., Alexandre J., Huang P. 2009. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nature Reviews, 8: 579-591.
  • 42. Ramiro-Cortés Y., Guemez-Gamboa A., Morán J. 2011. Reactive oxygen species participate in the p38-mediated apoptosis induced by potassium deprivation and staurosporine in cerebellar granule neurons. International Journal of Biochemistry & Cell Biology, 43(9): 1373-1382.
  • 43. Bouché M., Dahm G., Wantz M., Fournel S., Acharda T., Bellemin-Laponnaz S. 2016. Platinum(IV) N-heterocyclic carbene complexes: their synthesis, characterisation and cytotoxic activity. Dalton Transactions, 45(28): 11362–11368.
  • 44. Sergent C., Franco N., Chapusot C., Lizard-Nacol S., Isambert N., Correia M., Chauffert B. 2002. Human colon cancer cells surviving high doses of cisplatin or oxaliplatin in vitro are not defective in DNA mismatch repair proteins. Cancer Chemotherapy and Pharmacology, 49(6): 445–452.
  • 45. Shen D.-W., Cardarelli Hwang C.J., Cornwell M., Richert N., Ishii S., Pastan I., Gottesman M.M. 1986. Multiple drug-resistant human KB carcinoma cells independently selected for high-level resistance to colchicine, adriamycin, or vinblastine show changes in expression of specific proteins.. Journal of Biological Chemistry, 261: 7762–7770.
  • 46. Chekkat N., Dahm G., Chardon E., Wantz M., Sitz J., Decossas M., Lambert O., Frisch B., Rubbiani R., Gasser G., Guichard G., Fournel S., Bellemin-Laponnaz S. 2016. N-Heterocyclic Carbene–Polyethylenimine Platinum Complexes with Potent in Vitro and in Vivo Antitumor Efficacy. Bioconjugate Chemistry, 27(8): 1942−194.
  • 47. Tisato F., Marzano C., Porchia M., Pellei M., Santini C. 2010. Copper in diseases and treatments, and copper‐based anticancer strategies. Medicinal Research Reviews, 30(4): 708–749.
  • 48. Wang T., Guo Z. 2006. Copper in Medicine: Homeostasis, Chelation Therapy and Antitumor Drug Design. Current Medicinal Chemistry, 13(5): 525–537.
  • 49. Marzano C., Pellei M., Tisato F., Santini C. 2009. Anti-Cancer Agents. Medicinal Chemistry, 9(2): 185–211.
  • 50. Teyssot M.L., Jarrousse A.S., Chevry A., De Haze A., Beaudoin C., Manin M., Nolan S.P,. Diez-Gonzalez S., Morel L., Gautier A. 2009. Toxicity of Copper(I)–NHC Complexes Against Human Tumor Cells: Induction of Cell Cycle Arrest, Apoptosis, and DNA Cleavage. Chemistry A European Journal, 15(2): 314–318.
  • 51. Ruiz-Azuara L., Bravo-Gomez M.E. 2010. Copper Compounds in Cancer Chemotherapy. Current Medicinal Chemistry, 17(31): 3606–3615.
  • 52. Bowen R.J., Navarro M., Shearwood A.M., Healy P.C., Skelton B.W., Filipovska A., Berners-Price S.J. 2009. 1:2 Adducts of copper(I) halides with 1,2-bis(di-2-pyridylphosphino)ethane: solid state and solution structural studies and antitumour activity. Dalton Transactions, 2009(48): 10861–10870.
  • 53. Teyssot M.L., Jarrousse A.S., Manin M., Chevry A., Roche S., Norre F., Beaudoin C., Morel L., Boyer D., Mahiou R., Gautier A. 2009. Metal-NHC complexes: a survey of anti-cancer properties. Dalton Transactions, 2009(35): 6894–6902.
  • 54. Pellei M., Gandin V., Marinelli M., Marzano C., Yousufuddin M., Dias H.V.R., Santini C. 2012. Synthesis and Biological Activity of Ester- and Amide-Functionalized Imidazolium Salts and Related Water-Soluble Coinage Metal N-Heterocyclic Carbene Complexes. Inorganic Chemistry, 51(12): 9873–9882.
  • 55. Yang P., Guo M. 1999. Interactions of organometallic anticancer agents with nucleotides and DNA. Coordination Chemistry Reviews, 185–186: 189–211.
  • 56. Bertrand B., Romanov A.S., Brooks M., Davis J., Schmidt C., Ott I., O’Connell M., Bochmann M. 2017. Synthesis, structure and cytotoxicity of cyclic (alkyl)(amino) carbene and acyclic carbene complexes of group 11 metals. Dalton Transactions, 46: 15875-15887.
  • 57. Streciwilk W., Hackenberg F., Muller-Bunz H., Tacke M. 2014. Synthesis and cytotoxicity studies of p-benzyl substituted NHC–copper(I) bromide derivatives. Polyhedron 80: 3–9.
  • 58. Walther W., Fichtner I., Hackenberg F., Streciwilk W., Tacke M. 2014. In Vitro and In Vivo Investigations into the Carbene Gold Chloride and Thioglucoside Anticancer Drug Candidates NHC-AuCl and NHC-AuSR. Letters in Drug Design & Discovery, 11(2):825-832.
  • 59. Pellei M., Gandin V., Marinelli M., Orsetti A., Del Bello F., Santini C., Marzano C. 2015. Novel triazolium based 11th group NHCs: synthesis, characterization and cellular response mechanisms. Dalton Transactions, 44:21041–21052.
  • 60. Pizarro A.M., Sadler P.J. 2009. Unusual DNA binding modes for metal anticancer complexes. Biochimie, 91(10): 1198-1211.
  • 61. Ehrenfeld G.M., Shipley J.B., Heimbrook D.C., Sugiyama H., Long E.C., Van B.J.H., Van M.G.A., Oppenheimer N.J., Hecht S.M. 1987. Copper-Dependent Cleavage of DNA by Bleomycin. Biochemistry, 26: 931-942.
Birincil Dil tr
Konular Fen
Bölüm Derleme Makale
Yazarlar

Orcid: 0000-0001-8496-6782
Yazar: Aydın AKTAŞ (Sorumlu Yazar)
Kurum: İNÖNÜ ÜNİVERSİTESİ
Ülke: Turkey


Tarihler

Yayımlanma Tarihi : 28 Haziran 2019

Bibtex @derleme { bitlisfen480144, journal = {Bitlis Eren Üniversitesi Fen Bilimleri Dergisi}, issn = {2147-3129}, eissn = {2147-3188}, address = {}, publisher = {Bitlis Eren Üniversitesi}, year = {2019}, volume = {8}, pages = {713 - 724}, doi = {10.17798/bitlisfen.480144}, title = {Platin ve Bakır Temelli N-Heterosiklik Karben (NHC) Komplekslerinin Antikanser Özellikleri ve Etki Mekanizmaları}, key = {cite}, author = {AKTAŞ, Aydın} }
APA AKTAŞ, A . (2019). Platin ve Bakır Temelli N-Heterosiklik Karben (NHC) Komplekslerinin Antikanser Özellikleri ve Etki Mekanizmaları. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi , 8 (2) , 713-724 . DOI: 10.17798/bitlisfen.480144
MLA AKTAŞ, A . "Platin ve Bakır Temelli N-Heterosiklik Karben (NHC) Komplekslerinin Antikanser Özellikleri ve Etki Mekanizmaları". Bitlis Eren Üniversitesi Fen Bilimleri Dergisi 8 (2019 ): 713-724 <https://dergipark.org.tr/tr/pub/bitlisfen/issue/46476/480144>
Chicago AKTAŞ, A . "Platin ve Bakır Temelli N-Heterosiklik Karben (NHC) Komplekslerinin Antikanser Özellikleri ve Etki Mekanizmaları". Bitlis Eren Üniversitesi Fen Bilimleri Dergisi 8 (2019 ): 713-724
RIS TY - JOUR T1 - Platin ve Bakır Temelli N-Heterosiklik Karben (NHC) Komplekslerinin Antikanser Özellikleri ve Etki Mekanizmaları AU - Aydın AKTAŞ Y1 - 2019 PY - 2019 N1 - doi: 10.17798/bitlisfen.480144 DO - 10.17798/bitlisfen.480144 T2 - Bitlis Eren Üniversitesi Fen Bilimleri Dergisi JF - Journal JO - JOR SP - 713 EP - 724 VL - 8 IS - 2 SN - 2147-3129-2147-3188 M3 - doi: 10.17798/bitlisfen.480144 UR - https://doi.org/10.17798/bitlisfen.480144 Y2 - 2019 ER -
EndNote %0 Bitlis Eren Üniversitesi Fen Bilimleri Dergisi Platin ve Bakır Temelli N-Heterosiklik Karben (NHC) Komplekslerinin Antikanser Özellikleri ve Etki Mekanizmaları %A Aydın AKTAŞ %T Platin ve Bakır Temelli N-Heterosiklik Karben (NHC) Komplekslerinin Antikanser Özellikleri ve Etki Mekanizmaları %D 2019 %J Bitlis Eren Üniversitesi Fen Bilimleri Dergisi %P 2147-3129-2147-3188 %V 8 %N 2 %R doi: 10.17798/bitlisfen.480144 %U 10.17798/bitlisfen.480144
ISNAD AKTAŞ, Aydın . "Platin ve Bakır Temelli N-Heterosiklik Karben (NHC) Komplekslerinin Antikanser Özellikleri ve Etki Mekanizmaları". Bitlis Eren Üniversitesi Fen Bilimleri Dergisi 8 / 2 (Haziran 2019): 713-724 . https://doi.org/10.17798/bitlisfen.480144
AMA AKTAŞ A . Platin ve Bakır Temelli N-Heterosiklik Karben (NHC) Komplekslerinin Antikanser Özellikleri ve Etki Mekanizmaları. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi. 2019; 8(2): 713-724.
Vancouver AKTAŞ A . Platin ve Bakır Temelli N-Heterosiklik Karben (NHC) Komplekslerinin Antikanser Özellikleri ve Etki Mekanizmaları. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi. 2019; 8(2): 724-713.