Synthesis of Beta-Carboline Derivatives


Öncüoğlu S.

8th International Bahçeşehir University (BAU) Drug Design Congress, İstanbul, Turkey, 15 - 17 December 2022, pp.0-1

  • Publication Type: Conference Paper / Summary Text
  • City: İstanbul
  • Country: Turkey
  • Page Numbers: pp.0-1
  • Dokuz Eylül University Affiliated: Yes

Abstract

Synthesis of Beta-Carboline derivatives

Serkan Öncüoğlu1 ,  Alper Köse1 ,  Emre Gitgör1

1Dokuz Eylul University Faculty of Science Department of Chemistry


Introduction: Phosphodiesterase type 5 (PDE5) is a key enzyme involved in theregulation of cGMP-specific signaling pathways by catalyzing thehydrolysis of the cyclic nucleotide cGMP into guanosine monophosphates.It’s an essential regulator in normal physiologicalprocesses such as smooth muscle contraction and relaxation and it isthe major PDE isozyme in penile corpus cavernosum tissue that playsa key role in the control of penile erection. Tadalafil is anorally active tetrahydro-b-carboline (THBC) derivative with PDE5inhibitory properties that is marketed for the treatment of maleerectile dysfunction. Its local vasodilatation action is mediatedthrough high levels of cGMP in male corpus cavernosum. Azatoxin and derivatives there of formula B-D are illustrative of a new class of antitumor drugs that are topoisomerase II (top 2) inhibitors. The pharmacophore inhibits the catalytic activity of the purified enzyme but does not unwind relaxed or supercoiled DNA.

Methods: Beta-carboline derivative was formed as a result of sequential reactions by leaving L-tryptophan. Then, new tadalafil and azatoxin-like compounds were synthesized by forming the fourth ring on this compound

Synthesis Plan

Synthesis of Beta-Carboline derivatives

Serkan Öncüoğlu1 ,  Alper Köse1 ,  Emre Gitgör1

1Dokuz Eylul University Faculty of Science Department of Chemistry


Introduction: Phosphodiesterase type 5 (PDE5) is a key enzyme involved in theregulation of cGMP-specific signaling pathways by catalyzing thehydrolysis of the cyclic nucleotide cGMP into guanosine monophosphates.It’s an essential regulator in normal physiologicalprocesses such as smooth muscle contraction and relaxation and it isthe major PDE isozyme in penile corpus cavernosum tissue that playsa key role in the control of penile erection. Tadalafil is anorally active tetrahydro-b-carboline (THBC) derivative with PDE5inhibitory properties that is marketed for the treatment of maleerectile dysfunction. Its local vasodilatation action is mediatedthrough high levels of cGMP in male corpus cavernosum. Azatoxin and derivatives there of formula B-D are illustrative of a new class of antitumor drugs that are topoisomerase II (top 2) inhibitors. The pharmacophore inhibits the catalytic activity of the purified enzyme but does not unwind relaxed or supercoiled DNA.

Methods: Beta-carboline derivative was formed as a result of sequential reactions by leaving L-tryptophan. Then, new tadalafil and azatoxin-like compounds were synthesized by forming the fourth ring on this compound


Results and Discussion: Some derivatives have been synthesized. Studies are ongoing to test the biological affinities of these compounds. It is aimed to derivatize compounds according to the recommendations of in silico studies

Conclusions: Beta carboline derivatives, which can be topoisomerase 2 inhibitors and phosphodiesterase 5 inhibitors, have been synthesized

Keywords
 : azatoxin ,  PDE5 inhibitors ,  tadalafil ,  topoisomerase inhibitors

Results and Discussion: Some derivatives have been synthesized. Studies are ongoing to test the biological affinities of these compounds. It is aimed to derivatize compounds according to the recommendations of in silico studies

Conclusions: Beta carboline derivatives, which can be topoisomerase 2 inhibitors and phosphodiesterase 5 inhibitors, have been synthesized

Keywords
 : azatoxin ,  PDE5 inhibitors ,  tadalafil ,  topoisomerase inhibitors

Synthesis of Beta-Carboline derivatives

Serkan Öncüoğlu1 ,  Alper Köse1 ,  Emre Gitgör1

1Dokuz Eylul University Faculty of Science Department of Chemistry


Introduction: Phosphodiesterase type 5 (PDE5) is a key enzyme involved in theregulation of cGMP-specific signaling pathways by catalyzing thehydrolysis of the cyclic nucleotide cGMP into guanosine monophosphates.It’s an essential regulator in normal physiologicalprocesses such as smooth muscle contraction and relaxation and it isthe major PDE isozyme in penile corpus cavernosum tissue that playsa key role in the control of penile erection. Tadalafil is anorally active tetrahydro-b-carboline (THBC) derivative with PDE5inhibitory properties that is marketed for the treatment of maleerectile dysfunction. Its local vasodilatation action is mediatedthrough high levels of cGMP in male corpus cavernosum. Azatoxin and derivatives there of formula B-D are illustrative of a new class of antitumor drugs that are topoisomerase II (top 2) inhibitors. The pharmacophore inhibits the catalytic activity of the purified enzyme but does not unwind relaxed or supercoiled DNA.

Methods: Beta-carboline derivative was formed as a result of sequential reactions by leaving L-tryptophan. Then, new tadalafil and azatoxin-like compounds were synthesized by forming the fourth ring on this compound


Results and Discussion: Some derivatives have been synthesized. Studies are ongoing to test the biological affinities of these compounds. It is aimed to derivatize compounds according to the recommendations of in silico studies

Conclusions: Beta carboline derivatives, which can be topoisomerase 2 inhibitors and phosphodiesterase 5 inhibitors, have been synthesized

Keywords
 : azatoxin ,  PDE5 inhibitors ,  tadalafil ,  topoisomerase inhibitors

Beta-Karbolin türevlerinin sentezi

Serkan Öncüoğlu , Alper Köse , Emre Gitgör

Dokuz Eylül Üniversitesi Fen Fakültesi Kimya Bölümü

Giriş: Fosfodiesteraz tip 5 (PDE5), siklik nükleotit cGMP'nin guanozin monofosfatlara hidrolizini katalize ederek cGMP'ye özgü sinyal yollarının düzenlenmesinde yer alan anahtar bir enzimdir. Düz kas kasılması ve gevşemesi gibi normal fizyolojik süreçlerde temel bir düzenleyicidir ve penil ereksiyonun kontrolünde önemli bir rol oynayan penil korpus kavernozum dokusundaki majör PDE izozim. Tadalafil, erkek erektil disfonksiyonun tedavisi için pazarlanan, PDE5 inhibe edici özelliklere sahip, anoral olarak aktif tetrahidro-b-karbolin (THBC) türevidir. Yerel vazodilatasyon etkisine, erkek korpus kavernozumdaki yüksek cGMP seviyeleri aracılık eder. Azatoksin ve B-D formülünün türevleri, topoizomeraz II (ilk 2) inhibitörleri olan yeni bir antitümör ilaç sınıfının örnekleridir. Farmakofor, saflaştırılmış enzimin katalitik aktivitesini inhibe eder, ancak gevşemiş veya aşırı kıvrılmış DNA'yı çözmez.

Yöntemler: Beta-karbolin türevi, L-triptofandan başlayarak sıralı reaksiyonlar sonucunda oluştu. Daha sonra bu bileşik üzerinde dördüncü halka oluşturularak yeni tadalafil ve azatoksin benzeri bileşikler sentezlendi.

Sentez Planı

 



Sonuç ve Tartışma: Bazı türevler sentezlendi. Bu bileşiklerin biyolojik afinitelerini test etmek için çalışmalar devam etmektedir. Bileşiklerin in silico çalışmaların tavsiyelerine göre türetilmesi amaçlanmaktadır.

 

Sonuç: Topoizomeraz 2 inhibitörü ve fosfodiesteraz 5 inhibitörü olabilen beta karbolin türevleri sentezlendi

 

Anahtar Kelimeler : azotoksin , PDE5 inhibitörleri , tadalafil , topoizomeraz inhibitörleri