Synthesis and biological evaluation of chalcone-triazole hybrid derivatives as 15-LOX inhibitors

Abstract

An efficient aldol condensation/click reaction sequence is employed for the synthesis of chalcone-triazole-based derivatives in moderate to good yields. The ability of target compounds to inhibit 15-lipoxygenase enzyme was investigated and moderate to low inhibitory activities were observed for the synthesized compounds.

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

“…In the third step, 3-chloropentane-2,4-dione is added to the second step intermediate, N-carbamothioyl substituted benzamide ( 2 ), followed by reflux to afford the desired intermediates, N-(5-acetyl-4-methylthiazol-2-yl) substituted benzamides ( 3a – d ) via Hantzsch thiazole synthesis. The final step for the synthesis of the target chalcone-thiazole hybrids ( 4a – w ) is achieved using base catalyzed Claisen–Schmidt condensation reaction between benzamide thiazoyl ketones ( 3a – d ) and various substituted aromatic/heteroaromatic aldehydes in ethanol and 2.5 N NaOH . All the structures were confirmed using 1 H NMR, 13 C NMR, and HRMS (Supporting Information).…”

“…The final step for the synthesis of the target chalcone-thiazole hybrids (4a−w) is achieved using base catalyzed Claisen− Schmidt condensation reaction between benzamide thiazoyl ketones (3a−d) and various substituted aromatic/heteroaromatic aldehydes in ethanol and 2.5 N NaOH. 14 All the structures were confirmed using 1 H NMR, 13 C NMR, and HRMS (Supporting Information).…”

“…Chalcone (α,β-unsaturated ketone, collectively defined as an aromatic ketone and enone) based analogues are found in many natural compounds including turmeric in the form of curcumin, liquorice as isoliquiritigenin, and synthetic drugs such as homobutein . Chalcones are known to exhibit biological properties, such as antibacterial, anti-inflammatory, antioxidant, anticancer, antimalarial, and as carbonic anhydrase inhibitor. , Diarylsulfonylurea-chalcones, and di- o -prenylated chalcones have been reported as 5-LOX whereas chalcone-triazole hybrids as 15-LOX inhibitors. Phenylsulphonyl urenyl chalcones and 3,4-dihydroxychalcones act as dual 5-LOX/COX inhibitors.…”

Recent Advances in Bioactive Flavonoid Hybrids Linked by 1,2,3-Triazole Ring Obtained by Click Chemistry

“…Considering the anti-inflammatory properties of chalcones and triazoles, and in order to obtain new inhibitors of 15-lipoxigenase (15-LOX), chalcone hybrids 71a – 71c and 72a – 72i with a triazole ring on the ortho position and para position of the B ring of the chalcone scaffold, respectively, ( Figure 26 ) were synthesized [ 113 ]. Hybrids were obtained reacting O -propargyl-chalcones and benzyl halides by CuAAC reaction, giving rise to final products with 61–76% yield.…”