2-Amino-4-aryl thiazole: a promising scaffold identified as a potent 5-LOX inhibitor

Abstract

Human 5-lipoxygenase (5-LOX) is a target for asthma and allergy treatment. Zileuton is the only marketed drug targeting this enzyme (IC50 ∼ 1 μM). The current study identifies a promising lead molecule which could be improved to match the activity of zileuton.

Crystal structure of (E)-5-((4-chlorophenyl)diazenyl)-2-(5-(4-fluorophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-methylthiazole, C23H17ClFN5S2

“…Compounds bearing thiazole and pyrazole nuclei are found to have various antimicrobial activities such as antibacterial, antifungal and antitumor [1][2][3][4][5][6][7]. The asymmetric unit (cf.…”

Potential of pyrroquinazoline alkaloids fromAdhatoda vasicaNees. as inhibitors of 5-LOX – a computational and anin-vitrostudy

“…The alkaloids -Vasicine (98.2%) and Vasicinone (95.6%) (Natural Remedies, Bangalore, India) and control Zileuton (cayman chemical, Incalco, Italy) were subjected to an in-vitro 5-LOX enzyme inhibition assay as described by Sinha et al (2016). Semi-purified 5-LOX fraction extracted from the E.coli BL 21 bacteria containing pT3 plasmid coding recombinant human 5-LOX (Zhang et al, 1992) [a kind gift from Prof Olof Rådmark, Karolinska Institute, Stockholm, Sweden] was used in this assay.…”

Chalcone-Thiazole Hybrids: Rational Design, Synthesis, and Lead Identification against 5-Lipoxygenase

“…In analogy to our previous study, it was possible to incorporate the chalcone group along with thiazole for 5-LOX inhibition with a synergistic effect. As a result, molecules ( 4k : IC 50 = 0.07 ± 0.02 μM, 4n : IC 50 = 0.08 ± 0.05 μM) synthesized here are found to be 10–100 times better potent than previously reported thiazole molecules ( 2m : IC 50 = 0.9 ± 0.1 μM, 1d : IC 50 = 10 μM) by us and also better than Zileuton (IC 50 = 1.05 ± 0.03 μM). , SAR indicated that the presence of a greater number of electron donating groups, namely, methoxy and methyl, either in the vicinity of chalcone or both thiazole and chalcone contributed a synergistic effect and yielded highly active molecules. Pharmacophore elucidation revealed that the double bond of chalcone is one of the important reasons for hydrophobic centroid generation for inhibition.…”

“…Thiazoles are active constituents of various naturally occurring biologically significant compounds such as thiamine, mycothiazole, as well as synthetic drugs which act as antimicrobial, anti-inflammatory, anticancer, antiviral, and antitubercular. , Thiazol-4­(5H)-one derivatives, namely darbufelone and CI-987, are reported as dual COX/LOX inhibitors . Recently, thiazole bearing scaffolds, namely 2-amino-4-aryl thiazole-5-phenylmethanones, , N-aryl thiazole-2-amines, and 5-benzylidene-2-phenylthiazolinones, are identified as selective 5-LOX whereas aminothiazole pirinixic acids as dual 5-LOX/mPGES1 inhibitors.…”