2. Academic Validation
  3. Synthesis of novel thiazolyl hydrazone derivatives as potent dual monoamine oxidase-aromatase inhibitors

Synthesis of novel thiazolyl hydrazone derivatives as potent dual monoamine oxidase-aromatase inhibitors

  • Eur J Med Chem. 2022 Feb 5;229:114097. doi: 10.1016/j.ejmech.2021.114097.
Asaf Evrim Evren 1,  Demokrat Nuha 2,  Sam Dawbaa 3,  Begüm Nurpelin Sağlık 4,  Leyla Yurttaş 4
Affiliations

Affiliations

  • 1 Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470, Eskişehir, Turkey; Bilecik Şeyh Edebali University, Vocational School of Health Services, Department of Pharmacy Services, 11000, Bilecik, Turkey. Electronic address: [email protected].
  • 2 Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470, Eskişehir, Turkey; Eskisehir Technical University, Faculty of Science, Department of Chemistry, 26555, Eskişehir, Turkey.
  • 3 Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470, Eskişehir, Turkey; Department of Pharmacy, Faculty of Medicine and Health Sciences, Thamar University, Dhamar, Yemen.
  • 4 Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470, Eskişehir, Turkey.
PMID: 34998057 DOI: 10.1016/j.ejmech.2021.114097
Abstract

The inhibitory effects of 2-thiazolyl hydrazones on Monoamine Oxidase enzymes are known for a long time. In this study, a new series of 2-thiazolyl hydrazone derivatives were synthesized starting from 6-methoxy-2-naphthaldehyde. All of the synthesized compounds were investigated in terms of their Monoamine Oxidase (MAO) inhibitory effects and significant results were found. The results showed that compound 2j potently inhibited MAO-A and MAO-B, while compound 2t strongly and selectively inhibited MAO-B compared to standard drugs. Compounds 2k and 2q exhibited selective and satisfying inhibition on MAO-B. In the Aromatase inhibition studies of the compounds, it was determined that compounds 2q and 2u had high inhibitory properties. Molecular docking studies on MAO-A, MAO-B, and Aromatase enzymes were carried out for the aforementioned compounds. Additionally, molecular dynamics simulation was studied for compound 2q on MAO-B and Aromatase complexes. Finally, the Field-based QSAR study was developed and the structure-activity relationship (SAR) was explained. For the first time, dual inhibitors on MAO and Aromatase enzyme were investigated together. The aim of this approach is for finding the potential agents that do not cause the cognitive disorders and may even treat neurodegenerative symptoms, thus, the aim was reached successfully.

Keywords

2-Thiazolylhydrazones; Aromatase inhibition; Molecular docking; Molecular dynamic simulation; Monoamine oxidase inhibition; QSAR.

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