Potansiyel JNK1 İnhibe Edici Aktiviteye Sahip 2-((4-(dimetilamino)benziliden)amino)-5-metilfenol’ün Sentezi, Teorik Çalışmaları, Sitotoksisitesi

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 today’s clinics. In this study, a Schiff base 2-((4-(dimethylamino)benzylidene)amino)-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 (B3LYP/6-311g++(d,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.