Title : Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds - Sever_2021_Arch.Pharm.(Weinheim)__e2100294 |
Author(s) : Sever B , Turkes C , Altintop MD , Demir Y , Akalin Ciftci G , Beydemir S |
Ref : Arch Pharm (Weinheim) , :e2100294 , 2021 |
Abstract :
New hybrid thiazolyl-pyrazoline derivatives (4a-k) were obtained through a facile and versatile synthetic procedure, and their inhibitory effects on the human carbonic anhydrase (hCA) isoforms I and II as well as on acetylcholinesterase (AChE) were determined. All new thiazolyl-pyrazolines showed activity at nanomolar levels as hCA I, hCA II, and AChE inhibitors, with K(I) values in the range of 13.35-63.79, 7.01-115.80, and 17.89-48.05 nM, respectively. 1-[4-(4-Cyanophenyl)thiazol-2-yl]-3-(4-piperidinophenyl)-5-(4-fluorophenyl)-2-pyrazoline (4f) and 1-(4-phenylthiazol-2-yl)-3-(4-piperidinophenyl)-5-(4-fluorophenyl)-2-pyrazoline (4a) against hCAs and 1-[4-(4-chlorophenyl)thiazol-2-yl]-3-(4-piperidinophenyl)-5-(4-fluorophenyl)-2-pyrazoline (4d) and 1-[4-(4-nitrophenyl)thiazol-2-yl]-3-(4-piperidinophenyl)-5-(4-fluorophenyl)-2-pyrazoline (4b) against AChE were identified as highly potent inhibitors, superior to the standard drugs, acetazolamide and tacrine, respectively. Compounds 4a-k were also evaluated for their cytotoxic effects on the L929 mouse fibroblast (normal) cell line. Moreover, a comprehensive ligand-receptor interaction prediction was performed using the ADME-Tox, Glide XP, and MM-GBSA modules of the Schrodinger Small-Molecule Drug Discovery Suite to elucidate the potential binding modes of the new hybrid inhibitors against these metabolic enzymes. |
PubMedSearch : Sever_2021_Arch.Pharm.(Weinheim)__e2100294 |
PubMedID: 34569655 |
Sever B, Turkes C, Altintop MD, Demir Y, Akalin Ciftci G, Beydemir S (2021)
Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds
Arch Pharm (Weinheim)
:e2100294
Sever B, Turkes C, Altintop MD, Demir Y, Akalin Ciftci G, Beydemir S (2021)
Arch Pharm (Weinheim)
:e2100294