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

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.

Antimicrobial and Cytotoxic Evaluation of New Quinazoline Derivatives.

The synthesis of nine new quinazoline derivatives (2a-2i) and evaluation of their antimicrobial and cytotoxic activities were aims of the present work. For the synthesis of the compounds, 2-chloro-6,7-dimethoxyquinazolin-4-amine was used as the initial starting material. The intermediate product, 2-hydrazinyl-6,7- dimethoxyquinazolin-4-amine, was reacted with appropriate aromatic aldehydes to obtain 2-(2-benzylidenehydrazinyl)-6,7-dimethoxyquinazolin-4-amine derivatives as final compounds. The structures of the compounds were elucidated by (1)H- and (13)C-NMR, IR, and-MS analyses. The new pure compounds were evaluated for their potential antimicrobial and cytotoxic activities using in vitro microdilution and cell culture techniques, respectively. The compounds 2e and 2f may be promising candidates for the treatment of fungal infections with their activity and cytotoxicity.

Synthesis of new 1-phenyl-2-(4-substituted-piperazin-1-yl)-propanol derivatives and evaluation of their antidepressant-like effects.

In this study, we synthesized eight novel 1-phenyl-2-(4-substituted-piperazin-1-yl)-propanol derivatives and evaluated their antidepressant-like activities. The chemical structures of the synthesised compounds were elucidated by spectroscopy and elemental analyses. Potential antidepressant-like effects of the test compounds (20 mg kg(-1)) were investigated using the tail-suspension test and modified forced swimming test (MFST) in mice. Additionally, the spontaneous locomotor activity of the mice was assessed using the activity cage apparatus. Both the reference drug fluoxetine (20 mg kg(-1)) and the test compounds 3a-3e and 3g significantly shortened the immobility time of the mice in both the behavioural tests. These test compounds also increased the swimming time in MFST without any change in the climbing duration. Compounds 3c-3e and 3g were significantly more potent in inducing these effects than 3a and 3b. None of the compounds changed the locomotor activities of the animals, thus antidepressant-like effects of test compounds were specific. The findings support those of previous studies that reported antidepressant-like activities of aryl alkanol piperazine derivatives.