Synthesis, Theoretical Studies, Cytotoxicity of 2-((4-(Dimethylamino)Benzylidene)Amino)-5-Methylphenol with Potential JNK1 Inhibitory Activity

Oğuzhan Karaosmanoğlu; Halil Berber; Ülkü Dilek Uysal

Article Details

Synthesis, Theoretical Studies, Cytotoxicity of 2-((4-(Dimethylamino)Benzylidene)Amino)-5-Methylphenol with Potential JNK1 Inhibitory Activity

Authors:

Oğuzhan Karaosmanoğlu | Halil Berber | Ülkü Dilek Uysal

Publisher:

Süleyman Demirel University

Main Topics:

Sağlığın Geliştirilmesi

Journal:

Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi Vol.14 Issue 2, pp.253-272

Document Type:

Article

Publication Date:

8/2023

Document Language:

English

Document ID (Org No.):

2001293338

pISSN:

2146-247X

Keywords:

Abstract:

 Cisplatin, doxorubicin, hydroxycamptothecin, leucovorin, vincristine and 5-fluorouracil resistance of cancer cells are associated with the activities of C-Jun N-Terminal Kinase 1 JNK1. Inhibition of the JNK1 by pharmacological agents could be a beneficial attempt for reversing the chemoresistance of various cancer cells. However, there is no FDA-approved JNK inhibitor for safe use in clinics in todays clinics. In this study, a Schiff base 2-4-dimethylaminobenzylideneamino-5-methylphenol, 7S4 has been synthesized and characterized by 1H, 13C-NMR, FT-IR and elemental analysis. The stable geometry of 7S4 has been determined by DFT method with Gaussian09 program B3LYP6-311gd,p. The Gibbs Free energies, stable tautomer forms, H-bond, Mulliken charges, dipole moment, natural bond orbital NBO, HOMO, LUMO and band gap energy EGAP, molecular electrostatic potential MEP and solvent accessibility surface areas SASA have been calculated. Drug-likeness, anticancer and JNK1 inhibitory activities of 7S4 have been evaluated. Enol tautomer form of trans 7S4 was characterized as the most stable structure. 7S4 was observed to be a reactive compound in chemical reactions with a low EGAP value. In addition, high and low electron density regions of 7S4 are responsible for the establishment of chemical bonds in biological systems. 7S4 exhibited strong druggability with the agreement on Lipinski, Ghose, Veber, Egan, and Muegge rules. Cytotoxicity tests and molecular docking revealed that 7S4 poses a potential JNK1 inhibitor activity.

 Cisplatin, doxorubicin, hydroxycamptothecin, leucovorin, vincristine and 5-fluorouracil resistance of cancer cells are associated with the activities of C-Jun N-Terminal Kinase 1 JNK1. Inhibition of the JNK1 by pharmacological agents could be a beneficial attempt for reversing the chemoresistance of various cancer cells. However, there is no FDA-approved JNK inhibitor for safe use in clinics in todays clinics. In this study, a Schiff base 2-4-dimethylaminobenzylideneamino-5-methylphenol, 7S4 has been synthesized and characterized by 1H, 13C-NMR, FT-IR and elemental analysis. The stable geometry of 7S4 has been determined by DFT method with Gaussian09 program B3LYP6-311gd,p. The Gibbs Free energies, stable tautomer forms, H-bond, Mulliken charges, dipole moment, natural bond orbital NBO, HOMO, LUMO and band gap energy EGAP, molecular electrostatic potential MEP and solvent accessibility surface areas SASA have been calculated. Drug-likeness, anticancer and JNK1 inhibitory activities of 7S4 have been evaluated. Enol tautomer form of trans 7S4 was characterized as the most stable structure. 7S4 was observed to be a reactive compound in chemical reactions with a low EGAP value. In addition, high and low electron density regions of 7S4 are responsible for the establishment of chemical bonds in biological systems. 7S4 exhibited strong druggability with the agreement on Lipinski, Ghose, Veber, Egan, and Muegge rules. Cytotoxicity tests and molecular docking revealed that 7S4 poses a potential JNK1 inhibitor activity.

 Cisplatin, doxorubicin, hydroxycamptothecin, leucovorin, vincristine and 5-fluorouracil resistance of cancer cells are associated with the activities of C-Jun N-Terminal Kinase 1 JNK1. Inhibition of the JNK1 by pharmacological agents could be a beneficial attempt for reversing the chemoresistance of various cancer cells. However, there is no FDA-approved JNK inhibitor for safe use in clinics in todays clinics. In this study, a Schiff base 2-4-dimethylaminobenzylideneamino-5-methylphenol, 7S4 has been synthesized and characterized by 1H, 13C-NMR, FT-IR and elemental analysis. The stable geometry of 7S4 has been determined by DFT method with Gaussian09 program B3LYP6-311gd,p. The Gibbs Free energies, stable tautomer forms, H-bond, Mulliken charges, dipole moment, natural bond orbital NBO, HOMO, LUMO and band gap energy EGAP, molecular electrostatic potential MEP and solvent accessibility surface areas SASA have been calculated. Drug-likeness, anticancer and JNK1 inhibitory activities of 7S4 have been evaluated. Enol tautomer form of trans 7S4 was characterized as the most stable structure. 7S4 was observed to be a reactive compound in chemical reactions with a low EGAP value. In addition, high and low electron density regions of 7S4 are responsible for the establishment of chemical bonds in biological systems. 7S4 exhibited strong druggability with the agreement on Lipinski, Ghose, Veber, Egan, and Muegge rules. Cytotoxicity tests and molecular docking revealed that 7S4 poses a potential JNK1 inhibitor activity.

 Kanser hücrelerinin sisplatin, doksorubisin, hidroksikamptotesin, lökovorin, vinkristin ve 5-fluorourasil direnci, C-Jun N-Terminal Kinaz 1 JNK1 aktiviteleri ile ilişkilidir. JNK1in farmakolojik ajanlar tarafından inhibisyonu, çeşitli kanser hücrelerinin kemodirencini tersine çevirmek için yararlı bir yaklaşım olabilir. Ancak günümüz kliniklerinde güvenli kullanım için FDA onaylı bir JNK inhibitörü bulunmamaktadır. Bu çalışmada, bir Schiff bazı 2-4-dimetilaminobenzilidenamino-5-metilfenol, 7S4 sentezlenmiş ve 1H, 13C-NMR, FT-IR ve element analizi ile karakterize edilmiştir. 7S4ün kararlı geometrisi Gaussian09 programı B3LYP6-311gd,p ile DFT yöntemi ile belirlenmiştir. Gibbs Serbest enerjileri, kararlı tautomer formları, H-bağı, Mulliken yükleri, dipol momenti, doğal bağ orbital NBO, HOMO, LUMO ve bant boşluk enerjisi EGAP, moleküler elektrostatik potansiyel MEP ve çözücü erişilebilirlik yüzey alanları SASA hesaplanmıştır. 7S4ün ilaca benzerliği, antikanser ve JNK1 inhibitör aktiviteleri değerlendirilmiştir. Trans 7S4ün enol tautomer formu en kararlı yapı olarak nitelendirildi. 7S4ün düşük EGAP değeri ile kimyasal reaksiyonlarda reaktif bir bileşik olduğu gözlendi. Ayrıca 7S4ün yüksek ve düşük elektron yoğunluklu bölgeleri biyolojik sistemlerde kimyasal bağların kurulmasından sorumludur. 7S4, Lipinski, Ghose, Veber, Egan ve Muegge kurallarına ilişkin anlaşma ile güçlü uyuşturulabilirlik sergiledi. Sitotoksisite testleri ve moleküler kenetlenme, 7S4ün potansiyel bir JNK1 inhibitör aktivitesi oluşturduğunu ortaya çıkardı.

Article Details

Synthesis, Theoretical Studies, Cytotoxicity of 2-((4-(Dimethylamino)Benzylidene)Amino)-5-Methylphenol with Potential JNK1 Inhibitory Activity

Authors:

Oğuzhan Karaosmanoğlu | Halil Berber | Ülkü Dilek Uysal

Publisher:

Süleyman Demirel University

Main Topics:

Sağlığın Geliştirilmesi

Journal:

Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi Vol.14 Issue 2, pp.253-272

Document Type:

Article

Publication Date:

8/2023

Document Language:

English

Document ID (Org No.):

2001293338

pISSN:

2146-247X

Schiff bases

DFT method

JNK1 inhibitors

antitumor agents

druglikeness

molecular dockingSchiff bazları

DFT yöntemi

JNK1 inhibitörleri

antitümör ajanlar

ilaca benzerlik

moleküler kenetlenme

Issues

Article Details

Authors: Oğuzhan Karaosmanoğlu | Halil Berber | Ülkü Dilek Uysal

Publisher: Süleyman Demirel University

Main Topics: Sağlığın Geliştirilmesi

Journal: Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi Vol.14 Issue 2, pp.253-272

Document Type: Article

Publication Date: 8/2023

Document Language: English

Document ID (Org No.): 2001293338

pISSN: 2146-247X

Issues

Authors:

Oğuzhan Karaosmanoğlu | Halil Berber | Ülkü Dilek Uysal

Publisher:

Süleyman Demirel University

Main Topics:

Sağlığın Geliştirilmesi

Journal:

Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi Vol.14 Issue 2, pp.253-272

Document Type:

Article

Publication Date:

8/2023

Document Language:

English

Document ID (Org No.):

2001293338

pISSN:

2146-247X