Yamali, Cem; Engin, Feyza Sena; Bilginer, Sinan; Tugrak, Mehtap; Ozmen Ozgun, Dilan; Ozli, Gulsen; Levent, Serkan; Saglik, Begum Nurpelin; Ozkay, Yusuf; Gul, Halise Inci

Chalcones targeting neurodegenerative diseases have been known as attractive structures in drug design and discovery. In this study, phenothiazine-based chalcones as ChEs and MAOs inhibitors were designed and synthesized via base-catalyzed Claisen-Schmidt condensation, and chemical structures of the compounds were elucidated by NMRs and HRMS. Compounds 3 and 9 showed promising inhibition potency against AChE enzyme with IC50 values of 0.221 μM and 0.053 μM while compound 9 displayed remarkable inhibition potency toward MAO-B enzyme with IC50 value of 0.048 μM. Compound 9, as a dual-target inhibitor, selectively inhibited AChE and MAO-B enzymes. This promising behavior is an advantage for the compound since MAO-B and AChE inhibition have a role in Alzheimer's disease. Fused tricyclic ring systems such as phenothiazine incorporated with chalcone moiety being multitargeting ligands may help scientists for the rational design of novel lead compounds targeting neurodegenerative illnesses.

Çağlar Yavuz, Sevtap; Akkoç, Senem; Türkmenoğlu, Burçin; Sarıpınar, Emin

In a single reaction step, pyrimidine derivatives (4a-p) were synthesized from the triple reaction of aromatic aldehydes (1), ethyl cyanoacetate (2), and some guanyl hydrazone derivatives (3a-n). These compounds were tested as in vitro against two types of cancerous cell lines, namely, a human colon cancerous cell line (DLD-1) and a human breast cancerous cell line (MDA-MB-231). According to the obtained results, nearly all the compounds have cytotoxic activity in the tested cell lines. Especially, the compounds 4j, 4k, and 4n had a significant effect against DLD-1. Furthermore, compounds 4g, 4m, and 4o exhibited lower IC50 values compared to other synthesized compounds against MDA-MB-231. We hope that these compounds can be improved as anticancer agents in the future. Molecular docking was performed according to both topoisomerase I and N-acetyltransferase 1 proteins to examine theoretically the binding mode and site of pyrimidine compounds having the best activity.