Araştırma Makalesi
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Antiproliferative Activity of Pyrrolidine Derivatives compound in Colon Cancer Cells

Yıl 2022, Cilt: 4 Sayı: 1, 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, Cilt: 4 Sayı: 1, 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 Cilt: 4 Sayı: 1

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