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

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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

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