Conventional and microwave prompted synthesis, antioxidant, anticholinesterase activity screening and molecular docking studies of new quinolone-triazole hybrids


MERMER A., DEMİRBAŞ N. , SIRIN Y., USLU H., ÖZDEMİR Z., DEMİRBAŞ A.

BIOORGANIC CHEMISTRY, cilt.78, ss.236-248, 2018 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 78
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1016/j.bioorg.2018.03.017
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Sayfa Sayıları: ss.236-248

Özet

The synthesis of ethyl 4-oxo-1,4-dihydroquinoline-3-carboxylates (4, 5) was performed via the reaction of corresponding anilines with diethyl ethoxymethylenemalonate under conventional and also microwave promoted conditions. The treatment of 4 and 5 afforded the corresponding hydrazides (6 and 7). These hydrazides were converted to the corresponding carbo(thio) amides (9a-f and 10a-e) which were then subjected to an intramolecular cyclisation leading to the formation of quinolone-triazole hybrids (11a-f and 12a-e). The newly synthesized compounds were screened for their biological activities such as antioxidant capacity (AC) and acetylcholinesterase Activity. Inhibition of cholinesterases is an effective method to curb Alzheimer's disease, a progressive and fatal neurological disorder. A series of some novel quinolone derivatives were designed, synthesized, and their inhibitory effects on AChE were evaluated. We obtained our compounds and determined their anticholinesterase activities according to the Ellman's method. 9b and 10c showed the best AChE inhibition with 0.48 +/- 0.02 and 0.52 +/- 0.07, respectively. Docking studies were performed for the most active compounds (9b, 10c) and interaction modes with enzyme active sites were determined. As a result of these studies, a strong interaction between these compounds and the active sites of AChE enzyme was revealed. (C) 2018 Elsevier Inc. All rights reserved.