On another hand pyrazoles are widely

On another hand, pyrazoles, are widely found as the core structure in a large variety of compounds of great biological and pharmaceutical value exhibiting anti-HCV [11], antitumor [12], cytotoxic[13], and antioxidant activities [14]. Finally, 1,2,3-triazoles have attracted the interest of medicinal chemists due to their broad spectrum of applications in medicinal chemistry and biochemical [15]. Thus there are known as anti-tumoral [16] anticholinesterase [17], anti-5-lipoxygenase [18], anti-tyrosinase [19], and cytotoxic [20] agents. Encouraged by these data, we were prompted to explore versatile possibilities of access to novel hybrid conjugates associating these three aforementioned substructures within a same molecular target namely the 1,2,3-triazolo-coumarino[4,3-c]pyrazole and study their possible anticholinesterase, anti-5-lipoxygenase, anti-tyrosinase, and cytotoxic potentials.
Results and discussion
Conclusion In conclusion, this work reports the contribution to the valorization of coumarinopyrazole 2 as a coumarin derivative to access to new biaocative hybrid molecules. This coumarinopyrazole has been transformed into a mixture of propargylated regioisomers 3+3’, used as dipolarophiles for synthesizing the target coumarin-containing triazole via intermolecular 1,3-dipolar cycloaddition reaction. The newly prepared cycloadducts 4a-e and 5a-e have been tested for their possible anti-cholinesterase, anti-tyrosinase, anti 5-lipoxygenase and cytotoxic activities. The study of the SAR permitted to conclude in most cases the contribution of the added triazole moiety to the starting pyrazolocoumarin 2via the methylene group as a linker to improve or even to bring activity.
Materials and methods
Declaration of interest
Introduction Acute pancreatitis is a mild and self-limiting inflammatory condition of the SCH772984 TFA [1]. However, a significant mortality rate could be observed in severe necrotizing types such as acute necrotizing pancreatitis (ANP) [1]. The mortality rate of ANP has been reported at ∼10% in spite of the advances in essential medical care over the past decade including the improvement in fluid management and nutritional support [1]. The most common cause of ANP is the accumulation of gallbladder stones [2]. However, other factors, for example, ingested medicines, high blood calcium levels, and heavy alcohol consumption, have also been reported to induce ANP [2]. The typical symptom of ANP is sudden pain in either gradual or the upper abdomen and immediate medical attention is needed for a person with ANP [1,2]. Other exhibitions during ANP can include nausea, high body fever, and rapid heartbeats [1,2]. An early intervention with fluid resuscitation, usually within the first 24 h of disease onset, is critical for the treatment of ANP [3]. ANP can lead to severe pancreatic tissue injury and permanent death in a portion of pancreatic tissue, which is characterized as tissue necrosis [4]. In most cases, cell or tissue death due to necrosis is significantly distinguished from cell programmed death pathway apoptosis [5]. Rather than absorbing dead tissue/cells, necrosis can disrupt the integrity of cell membranes and unintentionally release products of damaged tissue fragments into extracellular space [5]. Consequently, excessive upregulation of inflammatory factors and cytokines, such as soluble cell adhesion molecules and leukocytes, can be induced and lead to failure and death of multiple organs [5]. Previous studies showed that leukotrienes (LTs) are a group of inflammatory mediators that play important roles in ANP-induced disease pathogenesis [4]. In LT biosynthesis, 5-lipoxygenase (5-LOX) exhibits critically catalytic functions: 1) dioxygenase activity and 2) leukotriene A4 (LTA4) synthase activity [6]. The evidence has been accumulating in support of the positive correlation between 5-LOX and the activation of anti-apoptotic factors in different types of cancers including lung, prostate, and colon [6].