Synthesis of new derivatives containing pyridine, investigation of MAO inhibitory activities and molecular docking studies.

In this study, novel pyridine-containing thiazolyl hydrazone derivatives were synthesized. Structure determinations of the compounds were performed using 1H NMR, 13C NMR and HRMS techniques. The biological activities of the compounds were evaluated against MAO enzymes by in vitro fluorometric method. As a result of activity studies, compound 3a showed selective inhibitory activity against MAO-B enzyme with IC50 = 0.088 + 0.003 µM. The selectivity index of this compound is greater than 1136. Molecular docking studies were carried out using 2V5Z crystal. It has been observed that docking studies and activity studies are in harmony.

Design, Synthesis and Biological Evaluation of a Novel Series of Thiadiazole- Based Anticancer Agents as Potent Angiogenesis Inhibitors.

BACKGROUND: Thiadiazole has attracted a great deal of interest as a versatile heterocycle for the discovery and development of potent anticancer agents. Thiadiazole derivatives exert potent antitumor activity against a variety of human cancer cell lines through various mechanisms. OBJECTIVE: The goal of this work was to design and synthesize thiadiazole-based anticancer agents with anti-angiogenic activity. METHODS: N-aryl-2-[(5-(aryl)amino-1,3,4-thiadiazol-2-yl)thio]acetamides (4a-r) were synthesized via the reaction of 5-(aryl)amino-1,3,4-thiadiazole-2(3H)-thiones with N-(aryl)-2-chloroacetamides in the presence of potassium carbonate. The compounds were investigated for their cytotoxic effects on three cancer (A549, HepG2, SH-SY5Y), two normal (HUVEC and 3T3-L1) cell lines using MTT and WST-1 assays. In order to examine whether the compounds have anti-angiogenic effects or not, HUVECs were cultured on matrigel matrix to create a vascular-like tube formation. RESULTS: Compounds 4d, 4m and 4n were more effective on A549 human lung adenocarcinoma cells than cisplatin. The IC50 values of compounds 4d, 4m and 4n for A549 cell line were found to be 7.82 ± 0.4, 12.5 ± 0.22, 10.1 ± 0.52 µM, respectively when compared with cisplatin (IC50= 20 ± 0.51 µM), whilst their IC50 values for HUVEC cell line were determined as 138.7 ± 0.84, 78 ± 0.44, 177.6 ± 0.2 µM, respectively after 48 h of the treatment. The concentrations (10-20-50 µM) of compounds 4d, 4e, 4l, 4m, 4n, 4q and 4r were found to inhibit vascular like tube formation. CONCLUSION: According to their anticancer and anti-angiogenic effects, compounds 4d, 4m and 4n may be potential anticancer agents for further in vivo studies.

Synthesis and AChE Inhibitory Activity of Novel Thiazolylhydrazone Derivatives.

Alzheimer's disease (AD) is the most common of the degenerative brain diseases and is described together with the impairment of cognitive function. Patients with AD lose the capability to code new memories, and life conditions are extremely difficult. The development of new drugs in this area continues at a great pace. A novel series of thiazole-piperazine hybrids, aimed against Alzheimer's disease (AD), have been synthesized. The structure identification of synthesized compounds was elucidated by 1HNMR, 13C-NMR, and LCMSMS spectroscopic methods. The inhibitory potential of the synthesized compounds on cholinesterase enzymes was investigated. The compounds 3a, 3c and 3i showed significant inhibitory activity on the acetylcholinesterase (AChE) enzyme. On the other hand, none of the compounds showed significant inhibitory activity on the butyrylcholinesterase (BChE) enzyme. In addition to enzyme inhibition studies, enzyme kinetic studies were performed to observe the effects of the most active inhibitor compounds on the substrate-enzyme relationship. In addition to in vitro tests, docking studies also indicated that compound 3c potentially acts as a dual binding site AChE inhibitor.