2-(((2,4-Dichlorophenyl)imino)methyl)-3,4-difluorophenol: X-ray, DFT, MEP, HOMO-LUMO, NLO, Hirshfeld Surfaces, ADMET Profiling, Target Identification, Antipsychotic Activity Against Dopamine D2 and Serotonin 5-HT2A Receptors

Songül Şahin

Makale detayları

2-(((2,4-Dichlorophenyl)imino)methyl)-3,4-difluorophenol: X-ray, DFT, MEP, HOMO-LUMO, NLO, Hirshfeld Surfaces, ADMET Profiling, Target Identification, Antipsychotic Activity Against Dopamine D2 and Serotonin 5-HT2A Receptors

Yazarlar:

Songül Şahin

Yayıncı:

Gazi University

Ana Başlıklar:

Engineering

Dergi:

Gazi University Journal of Science Vol.37 Issue 1, pp.90-117

Belge Tipi:

Makale

Yayın Tarihi:

1/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001300209

pISSN:

2147-1762

Anahtar kelimeler:

Özet:

 Halogenated compounds, especially fluorine and chlorine, play a key role in drug development. They account for a large proportion of all approved drug molecules. The importance of these two halogens stems from their remarkable effects on biological activity and pharmacokinetic properties. The study presented here aims to give the results obtained by the DFT methods and in silico medicinal evaluations of a newly synthesized small molecule. The small molecule belongs to the Schiff base class of organic compounds and is substituted with halogen atoms. The tetrahalogenated compound THSB Schiff base, 2-2,4-dichlorophenyliminomethyl-3,4-difluorophenol, was first synthesized via the classical condensation method and then characterized by spectroscopic techniques. The THSB optimized by the B3LYP method was evaluated in terms of geometrical parameters, surface area MEP and Hirshfeld analysis and secondary interaction analysis, NLO properties, and electronic properties HOMO-LUMO and UV-Vis. Second, THSB was evaluated regarding medicinal chemistry, physicochemical and pharmacokinetic properties, and toxicity ADMET. Then, we comprehensively investigated the potential biological targets of THSB. Using the results of the SwissSimilarity analysis, we investigated the antagonistic effects of THSB against serotonin 5-HT2A and dopamine D2 receptors. Docking results were compared with the known antipsychotics, clozapine and risperidone. THSB showed a higher antagonistic effect than clozapine for the D2 receptor. However, risperidone proved to be the most effective antagonist for both targets. The binding energies of THSB, risperidone, and clozapine were -8.30, -11.84, and -8.07 kcalmol, respectively, for D2; those of THSB, risperidone, and clozapine were -6.94, -11.47, and -10.10 kcalmol, respectively, for 5-HT2A.

 Halogenated compounds, especially fluorine and chlorine, play a key role in drug development. They account for a large proportion of all approved drug molecules. The importance of these two halogens stems from their remarkable effects on biological activity and pharmacokinetic properties. The study presented here aims to give the results obtained by the DFT methods and in silico medicinal evaluations of a newly synthesized small molecule. The small molecule belongs to the Schiff base class of organic compounds and is substituted with halogen atoms. The tetrahalogenated compound THSB Schiff base, 2-2,4-dichlorophenyliminomethyl-3,4-difluorophenol, was first synthesized via the classical condensation method and then characterized by spectroscopic techniques. The THSB optimized by the B3LYP method was evaluated in terms of geometrical parameters, surface area MEP and Hirshfeld analysis and secondary interaction analysis, NLO properties, and electronic properties HOMO-LUMO and UV-Vis. Second, THSB was evaluated regarding medicinal chemistry, physicochemical and pharmacokinetic properties, and toxicity ADMET. Then, we comprehensively investigated the potential biological targets of THSB. Using the results of the SwissSimilarity analysis, we investigated the antagonistic effects of THSB against serotonin 5-HT2A and dopamine D2 receptors. Docking results were compared with the known antipsychotics, clozapine and risperidone. THSB showed a higher antagonistic effect than clozapine for the D2 receptor. However, risperidone proved to be the most effective antagonist for both targets. The binding energies of THSB, risperidone, and clozapine were -8.30, -11.84, and -8.07 kcalmol, respectively, for D2; those of THSB, risperidone, and clozapine were -6.94, -11.47, and -10.10 kcalmol, respectively, for 5-HT2A.

 Halogenated compounds, especially fluorine and chlorine, play a key role in drug development. They account for a large proportion of all approved drug molecules. The importance of these two halogens stems from their remarkable effects on biological activity and pharmacokinetic properties. The study presented here aims to give the results obtained by the DFT methods and in silico medicinal evaluations of a newly synthesized small molecule. The small molecule belongs to the Schiff base class of organic compounds and is substituted with halogen atoms. The tetrahalogenated compound THSB Schiff base, 2-2,4-dichlorophenyliminomethyl-3,4-difluorophenol, was first synthesized via the classical condensation method and then characterized by spectroscopic techniques. The THSB optimized by the B3LYP method was evaluated in terms of geometrical parameters, surface area MEP and Hirshfeld analysis and secondary interaction analysis, NLO properties, and electronic properties HOMO-LUMO and UV-Vis. Second, THSB was evaluated regarding medicinal chemistry, physicochemical and pharmacokinetic properties, and toxicity ADMET. Then, we comprehensively investigated the potential biological targets of THSB. Using the results of the SwissSimilarity analysis, we investigated the antagonistic effects of THSB against serotonin 5-HT2A and dopamine D2 receptors. Docking results were compared with the known antipsychotics, clozapine and risperidone. THSB showed a higher antagonistic effect than clozapine for the D2 receptor. However, risperidone proved to be the most effective antagonist for both targets. The binding energies of THSB, risperidone, and clozapine were -8.30, -11.84, and -8.07 kcalmol, respectively, for D2; those of THSB, risperidone, and clozapine were -6.94, -11.47, and -10.10 kcalmol, respectively, for 5-HT2A.

 Halogenated compounds, especially fluorine and chlorine, play a key role in drug development. They account for a large proportion of all approved drug molecules. The importance of these two halogens stems from their remarkable effects on biological activity and pharmacokinetic properties. The study presented here aims to give the results obtained by the DFT methods and in silico medicinal evaluations of a newly synthesized small molecule. The small molecule belongs to the Schiff base class of organic compounds and is substituted with halogen atoms. The tetrahalogenated compound THSB Schiff base, 2-2,4-dichlorophenyliminomethyl-3,4-difluorophenol, was first synthesized via the classical condensation method and then characterized by spectroscopic techniques. The THSB optimized by the B3LYP method was evaluated in terms of geometrical parameters, surface area MEP and Hirshfeld analysis and secondary interaction analysis, NLO properties, and electronic properties HOMO-LUMO and UV-Vis. Second, THSB was evaluated regarding medicinal chemistry, physicochemical and pharmacokinetic properties, and toxicity ADMET. Then, we comprehensively investigated the potential biological targets of THSB. Using the results of the SwissSimilarity analysis, we investigated the antagonistic effects of THSB against serotonin 5-HT2A and dopamine D2 receptors. Docking results were compared with the known antipsychotics, clozapine and risperidone. THSB showed a higher antagonistic effect than clozapine for the D2 receptor. However, risperidone proved to be the most effective antagonist for both targets. The binding energies of THSB, risperidone, and clozapine were -8.30, -11.84, and -8.07 kcalmol, respectively, for D2; those of THSB, risperidone, and clozapine were -6.94, -11.47, and -10.10 kcalmol, respectively, for 5-HT2A.

Makale detayları

2-(((2,4-Dichlorophenyl)imino)methyl)-3,4-difluorophenol: X-ray, DFT, MEP, HOMO-LUMO, NLO, Hirshfeld Surfaces, ADMET Profiling, Target Identification, Antipsychotic Activity Against Dopamine D2 and Serotonin 5-HT2A Receptors

Yazarlar:

Songül Şahin

Yayıncı:

Gazi University

Ana Başlıklar:

Engineering

Dergi:

Gazi University Journal of Science Vol.37 Issue 1, pp.90-117

Belge Tipi:

Makale

Yayın Tarihi:

1/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001300209

pISSN:

2147-1762

Fluorine compound

Chlorine compound

Schiff base

D2 receptor

5-HT2A receptor

Sayı

Makale detayları

2-(((2,4-Dichlorophenyl)imino)methyl)-3,4-difluorophenol: X-ray, DFT, MEP, HOMO-LUMO, NLO, Hirshfeld Surfaces, ADMET Profiling, Target Identification, Antipsychotic Activity Against Dopamine D2 and Serotonin 5-HT2A Receptors

Yazarlar: Songül Şahin

Yayıncı: Gazi University

Ana Başlıklar: Engineering

Dergi: Gazi University Journal of Science Vol.37 Issue 1, pp.90-117

Belge Tipi: Makale

Yayın Tarihi: 1/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001300209

pISSN: 2147-1762

Fluorine compound

Chlorine compound

Schiff base

D2 receptor

5-HT2A receptor

Sayı

Yazarlar:

Songül Şahin

Yayıncı:

Gazi University

Ana Başlıklar:

Engineering

Dergi:

Gazi University Journal of Science Vol.37 Issue 1, pp.90-117

Belge Tipi:

Makale

Yayın Tarihi:

1/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001300209

pISSN:

2147-1762