Araştırma Makalesi
BibTex RIS Kaynak Göster

Antiproliferative Activity of Pyrrolidine Derivatives compound in Colon Cancer Cells

Yıl 2022, , 1 - 5, 27.02.2022
https://doi.org/10.52827/hititmedj.924278

Öz

Objective: Anti-cancer drug research plays an important role for chemotherapeutic treatments in various types of cancer. Pyrolidine derived compounds have been reported by many researchers to be a potent anti-cancer compound. It is aimed to investigate the effects of pyrolidine-derived compounds that are thought to be new drug candidates with antiproliferative activity on DLD-1 and CCD-18CO cell lines.

Material and Methods: The antiproliferative activity of the pyrrolidine-derived compound was determined for 24 hours at different concentrations (25-100 µM) on DLD-1 (human colon cancer) and CCD-18CO (normal colon fibroblast) cell lines by comparing MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5 Diphenyltetrazolium bromide) and RTCA (real-time cell analysis) assays. The significance of the differences between data sets in the MTT assay was analyzed statistically by ANOVA with SPSS 20.0 program for DLD-1 and CCD-18CO cell lines.

Results: It has been determined that pyrrolidine-derived compounds reduce the number of DLD-1 cancer cells according to negative control with the MTT method and suppress the DLD-1 cell according to the RTCA assay results. Thus, the compounds have been shown to inhibit cell proliferation and have antiproliferative activity.

Conclusion: Pyrrolidine-derived compounds will be the first step for antiproliferative activity studies in DLD-1 cancer cells and will guide the next studies.

Destekleyen Kurum

Amasya Üniversitesi

Proje Numarası

FMB-BAP 18-0333

Teşekkür

The authors would like to thank Hela Aguerbi (Hitit University) for the critical reading of the manuscript.

Kaynakça

  • 1. Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg 2009;22:191-197.
  • 2. Kuipers EJ, Rösch T, Bretthauer M. Colorectal cancer screening-optimizing current strategies and new directions. Nat Rev Clin Oncol 2013;10:130-142.
  • 3. Talib WH, Mahasneh AM. Antiproliferative activity of plant extracts used against cancer in traditional medicine. Sci Pharm 2010;78:33-45.
  • 4. Kuipers EJ, Grady WM, Lieberman D et al. Colorectal cancer. Nat Rev Dis Primers 2015;1:15065.
  • 5. Zięba A, Latocha M, Sochanik A, Nycz, A, Kuśmierz D, Synthesis and in vitro Antiproliferative Activity of Novel henyl RingSubstituted 5-Alkyl-12(H)-quino[3,4-b][1,4]benzothiazine Derivatives. Molecules (Basel, Switzerland) 2016;21:1455.
  • 6. Hati S, Tripathy S, Dutta PK et al. Spiro[pyrrolidine-3, 3-oxindole] as potent anti-breast cancer compounds: Their design, synthesis, biological evaluation and cellular target identification. Sci Rep 2016;6,32213.
  • 7. Tahata S, Yuan B, Kikuchi H, Takagi N, Hirano T, Toyoda H. Cytotoxic effects of pyrrolidine dithiocarbamate in small-cell lung cancer cells, alone and in combination with cisplatin. Int J Oncol 2014;45:1749-1759.
  • 8. Huang Y, Huang YX, Sun J, Yan CG. A [3+2] cycloaddition reaction for the synthesis of spiro[indoline-3,3′-pyrrolidines] and evaluation of cytotoxicity towards cancer cells. New Journal of Chemistry 2019;43:8903-8910.
  • 9. Çömlekçi E, Vejselova Sezer C, İzgördü H, Kutlu M. Ellajik Asidin İnsan Akciğer Kanseri Üzerine Antiproliferatif Etkinliklerinin in vitro Araştırılması. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi 2019;6:397-403.
  • 10. Zhang Y, Zhang Q, Wei F, Liu N. Progressive study of effects of erianin on anticancer activity. Onco Targets Ther 2019;12:5457-5465.
  • 11. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods 1983;65:55-63.
  • 12. Türker Şener L, Albeniz G, Dinç B, Albeniz I. iCELLigence realtime cell analysis system for examining the cytotoxicity of drugs to cancer cell lines. Exp Ther Med 2017;14:1866–1870.
  • 13. Elemes Y, Ragnarsson U. Synthesis of enantiopure α-deuteriated Boc-L-amino acids, Journal of the Chemical Society, Perkin Transactions 1996;1:537-540.
  • 14. Georgiou D, Toutountzoglou V, Muir KW, Hadjipavlou-Litina D, Elemes Y. Synthesis of sulfur containing dihydro-pyrrolo derivatives and their biological evaluation as antioxidants, Bioorganic and medicinal chemistry 2012;20:5103-5109.
  • 15. Pelit E, Oikonomou K, Gul M et al. α-Amination and the 5-exotrig cyclization reaction of sulfur-containing Schiff bases with Nphenyltriazolinedione and their anti-lipid peroxidation activity, Comptes Rendus Chimie 2017;20:424-434.
  • 16. Islam MS, Al-Majid AM, El-Senduny FF et al. Synthesis, anticancer activity, and molecular modeling of new halogenated spiro [pyrrolidine-thiazolo-oxindoles] derivatives. Applied Sciences 2020;10:2170.
  • 17. Zulfiqar S, Haroon M, Baig M et al. Synthesis, crystal structure, anti-cancer, anti-inflammatory anti-oxidant and quantum chemical studies of 4-(pyrrolidine-2, 5-dione-1-yl) phenol. Journal of Molecular Structure 2021;1224:129267.
  • 18. Sirin S, Duyar H, Aslım B, Seferoğlu Z. Synthesis and biological activity of pyrrolidine/piperidine substituted 3-amido-9-ethylcarobazole deriivatives. Journal of Molecular Structure 2021;1242: 130687.

Kolon Kanseri Hücrelerinde (DLD-1) Pirolidin Türevi Bileşiğin Antiproliferatif Aktivitesi

Yıl 2022, , 1 - 5, 27.02.2022
https://doi.org/10.52827/hititmedj.924278

Öz

Amaç: Anti-kanser ilaç araştırmaları, çeşitli kanser türlerinde kemoterapötik tedavilerde önemli bir rol oynamaktadır. Pirolidin türevi bileşiklerin birçok araştırmacı tarafından güçlü bir anti-kanser bileşiği olduğu bildirilmiştir. Antiproliferatif aktiviteye sahip yeni ilaç adayları olduğu düşünülen pirolidin türevi bileşiklerin DLD-1 ve CCD-18CO hücre hatları üzerindeki etkilerinin araştırılması amaçlanmıştır.


Gereç ve Yöntemler:
Pirolidin türevli bileşiklerin antiproliferatif aktivitesi DLD-1 (insan kolon kanseri) ve CCD-18CO (normal kolon fibroblast) hücre hatlarında karşılaştırılarak farklı konsantrasyonlarda (25-100 uM) MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5 Diphenyltetrazolium bromide) ve RTCA (gerçek zamanlı hücre analizi) deneyleri ile 24 saat boyunca incelendi. MTT deneyinde veri setleri arasındaki farkların önemi, DLD-1 ve CCD-18CO hücre hatlarında SPSS 20.0 programıyla ANOVA ile istatistiksel olarak analiz edildi.


Bulgular:
Pirolidin türevi bileşiklerin MTT yöntemi ile negatif kontrole göre DLD-1 kanser hücrelerinin sayısını azalttığı ve RTCA test sonuçlarına göre ise DLD-1 hücresinin baskılandığı belirlendi. Bu nedenle, bileşiklerin hücre proliferasyonunu inhibe ettiği ve antiproliferatif aktiviteye sahip olduğu gösterilmiştir.


Sonuç:
Pirolidin türevi bileşiklerin DLD-1 kanser hücrelerinde antiproliferatif aktivite çalışmaları için ilk adım olabileceği ve gelecekteki çalışmalara rehberlik edeceği düşünülmektedir.

Proje Numarası

FMB-BAP 18-0333

Kaynakça

  • 1. Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg 2009;22:191-197.
  • 2. Kuipers EJ, Rösch T, Bretthauer M. Colorectal cancer screening-optimizing current strategies and new directions. Nat Rev Clin Oncol 2013;10:130-142.
  • 3. Talib WH, Mahasneh AM. Antiproliferative activity of plant extracts used against cancer in traditional medicine. Sci Pharm 2010;78:33-45.
  • 4. Kuipers EJ, Grady WM, Lieberman D et al. Colorectal cancer. Nat Rev Dis Primers 2015;1:15065.
  • 5. Zięba A, Latocha M, Sochanik A, Nycz, A, Kuśmierz D, Synthesis and in vitro Antiproliferative Activity of Novel henyl RingSubstituted 5-Alkyl-12(H)-quino[3,4-b][1,4]benzothiazine Derivatives. Molecules (Basel, Switzerland) 2016;21:1455.
  • 6. Hati S, Tripathy S, Dutta PK et al. Spiro[pyrrolidine-3, 3-oxindole] as potent anti-breast cancer compounds: Their design, synthesis, biological evaluation and cellular target identification. Sci Rep 2016;6,32213.
  • 7. Tahata S, Yuan B, Kikuchi H, Takagi N, Hirano T, Toyoda H. Cytotoxic effects of pyrrolidine dithiocarbamate in small-cell lung cancer cells, alone and in combination with cisplatin. Int J Oncol 2014;45:1749-1759.
  • 8. Huang Y, Huang YX, Sun J, Yan CG. A [3+2] cycloaddition reaction for the synthesis of spiro[indoline-3,3′-pyrrolidines] and evaluation of cytotoxicity towards cancer cells. New Journal of Chemistry 2019;43:8903-8910.
  • 9. Çömlekçi E, Vejselova Sezer C, İzgördü H, Kutlu M. Ellajik Asidin İnsan Akciğer Kanseri Üzerine Antiproliferatif Etkinliklerinin in vitro Araştırılması. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi 2019;6:397-403.
  • 10. Zhang Y, Zhang Q, Wei F, Liu N. Progressive study of effects of erianin on anticancer activity. Onco Targets Ther 2019;12:5457-5465.
  • 11. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods 1983;65:55-63.
  • 12. Türker Şener L, Albeniz G, Dinç B, Albeniz I. iCELLigence realtime cell analysis system for examining the cytotoxicity of drugs to cancer cell lines. Exp Ther Med 2017;14:1866–1870.
  • 13. Elemes Y, Ragnarsson U. Synthesis of enantiopure α-deuteriated Boc-L-amino acids, Journal of the Chemical Society, Perkin Transactions 1996;1:537-540.
  • 14. Georgiou D, Toutountzoglou V, Muir KW, Hadjipavlou-Litina D, Elemes Y. Synthesis of sulfur containing dihydro-pyrrolo derivatives and their biological evaluation as antioxidants, Bioorganic and medicinal chemistry 2012;20:5103-5109.
  • 15. Pelit E, Oikonomou K, Gul M et al. α-Amination and the 5-exotrig cyclization reaction of sulfur-containing Schiff bases with Nphenyltriazolinedione and their anti-lipid peroxidation activity, Comptes Rendus Chimie 2017;20:424-434.
  • 16. Islam MS, Al-Majid AM, El-Senduny FF et al. Synthesis, anticancer activity, and molecular modeling of new halogenated spiro [pyrrolidine-thiazolo-oxindoles] derivatives. Applied Sciences 2020;10:2170.
  • 17. Zulfiqar S, Haroon M, Baig M et al. Synthesis, crystal structure, anti-cancer, anti-inflammatory anti-oxidant and quantum chemical studies of 4-(pyrrolidine-2, 5-dione-1-yl) phenol. Journal of Molecular Structure 2021;1224:129267.
  • 18. Sirin S, Duyar H, Aslım B, Seferoğlu Z. Synthesis and biological activity of pyrrolidine/piperidine substituted 3-amido-9-ethylcarobazole deriivatives. Journal of Molecular Structure 2021;1242: 130687.
Toplam 18 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Tıp Bilimleri
Bölüm Araştırma Makaleleri
Yazarlar

Seda Mesci 0000-0002-5440-302X

Melek Gül 0000-0002-0037-1202

Tuba Yıldırım 0000-0001-8575-4802

Proje Numarası FMB-BAP 18-0333
Yayımlanma Tarihi 27 Şubat 2022
Gönderilme Tarihi 21 Nisan 2021
Kabul Tarihi 28 Ekim 2021
Yayımlandığı Sayı Yıl 2022

Kaynak Göster

AMA Mesci S, Gül M, Yıldırım T. Antiproliferative Activity of Pyrrolidine Derivatives compound in Colon Cancer Cells. Hitit Medical Journal. Şubat 2022;4(1):1-5. doi:10.52827/hititmedj.924278