Z. Naturforsch. 2018; 73(2)b: 77–83 Ali Asadipour, Saeedeh Noushini, Setareh Moghimi, Mohammad Mahdavi, Hamid Nadri, Alireza Moradi, Shabnam Shabani, Loghman Firoozpour and Alireza Foroumadi* Synthesis and biological evaluation of chalcone-triazole hybrid derivatives as 15-LOX inhibitors https://doi.org/10.1515/znb-2017-0115 Received June 25, 2017; accepted October 15, 2017 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-lipoxy- genase enzyme was investigated and moderate to low inhibitory activities were observed for the synthesized compounds. Keywords: chalcone; lipoxygenase; quercetine; triazole. 1 Introduction Lipoxygenases (LOXs) are a heterogeneous family of non- heme, iron-oxidizing enzymes in animal and vegetal kingdoms, converting fatty acids and esters into their hydroperoxy analogs [1–4]. LOX proteins consist of a single polypeptide chain with two domains, including N-terminal domain and a large catalytic domain with non-heme iron [5]. There are three major isoforms of LOX in human body: 5-LOX, 12-LOX and 15-LOX. The numbers clearly show the positional specificity for oxygenation of polyunsaturated fatty acid, arachidonic acid (AA). The catalytic oxidation of the key substrate, AA, necessarily needs the conversion of the inactive form of the enzyme (Fe 3+ ) to the active form, ferric ion (Fe 2+ ) [6]. The products of this catalytic process (eicosanoids) result in inflam- matory mediators (lipoxins and leukotrienes), which are involved in etiology of certain disease such as cardiovas- cular diseases, cancer, asthma, psoriasis and rheuma- toid arthritis [7–9]. The ability of heterocyclic systems in preventing the single-electron transfer between Fe 3+ and Fe 2+ , consequently led to the activation of enzyme, has been widely considered in the literature as a signifi- cant mechanism for LOX inhibition [10]. Regarding the correlation between LOXs and inflammatory reactions, the inhibition of LOX by heterocyclic systems could be regarded as a treatment strategy of inflammatory and allergic diseases. Chalcone (PhCOCH=CHPh) is a privileged frame- work in medicinal chemistry regarding the broad spec- trum of pharmacological properties associated with this compound and its derivatives [11]. Meanwhile, hydroxy- lated chalcones manifest multiple prominent bioac- tivities [12–17] and are also the main precursor for the construction of biflavonoids [16, 17]. In this context, the excellent in vitro and in vivo anti-inflammatory activities of 2-hydroxy chalcones and flavones were presented by Alcaraz et al. in 1995 [18], which inspired us to design our project for the synthesis of novel chalcone-contain- ing compounds. 1,2,3-Triazole is an important heteroaromatic nucleus in pharmacological agents [19]. Relied on this fact, tria- zole is introduced as an indispensable anchor for the design and synthesis of novel therapeutic agents [20–24]. The potential of triazole-based compounds is that they have been reported in the literature as anti-inflammatory agents [25–27], because of their satisfactory binding affin- ity to the target enzyme [28–31]. The copper-catalyzed *Corresponding author: Alireza Foroumadi, Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, I.R. Iran; and Department of Medicinal Chemistry, Faculty of Pharmacy and Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, I.R. Iran, e-mail: aforoumadi@yahoo.com Ali Asadipour: Department of Medicinal Chemistry, Faculty of Pharmacy and Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, I.R. Iran Saeedeh Noushini, Setareh Moghimi, Shabnam Shabani and Loghman Firoozpour: Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, I.R. Iran Mohammad Mahdavi: Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, I.R. Iran Hamid Nadri and Alireza Moradi: Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, I.R. Iran Brought to you by | UCL - University College London Authenticated Download Date | 2/4/18 10:25 AM