Synthesis of a Water‐Soluble Pyrazole Curcumin Derivative: In Vitro and In Vivo AGE Inhibitory Activity and Its Mechanism

Abstract

The new chemical entity, water‐soluble pyrazole curcumin derivative (PyCurOAc) was designed, synthesized and characterized for the purpose of inhibition of AGE formation. The compound showed an excellent in vitro AGEs inhibition activity than curcumin itself as well as the standard. Further, the AGE inhibition activity was substantiated in vivo using C.elegans as an animal model. The mechanistic investigation for the inhibition of AGEs with PyCurOAc was studied with glod‐4 expressions in C.elegans and glucose trapping method. This study suggests that the synthesized compound could be used to treat the formation of AGEs in hyperglycemic nematodes and higher animals.

Recent Updates in Curcumin Pyrazole and Isoxazole Derivatives: Synthesis and Biological Application

“…Oxidation potentials and radical scavenging properties of semicarbazone and pyrazole curcumin derivatives were examined and exhibited low dose modifying factors (DMF). [78] It also endorses membrane homeostasis subsequent TBI, which can promote a modern line of non-invasive curative treatment for TBI patients by endogenous up-regulation of molecules imperative for neural refurbish and flexibility.…”

“…Additionally, the AGE inhibition activity was substantiated in vivo using C. elegans as an animal model. [78]…”

Curcuminoids versus Pyrazole‐Modified Analogues: Synthesis and Cytotoxicity against HepG2 Cancer Cell Line

“…The observations are similar to the reported results in previous works, in which pyrazole-based analogues showed better cytotoxicity profiles due to their improved solubility and stability. [6,15,16,[18][19][20] Labbozzetta et al reported that curcuminoids sensitize the human hepatic cancer cells to apoptotic effects while pyrazole curcuminoids lacked the interaction with cell -SH groups and glutathione. [13] In other words, the detoxification mechanism is not required for an increased anticancer potency of pyrazole candidates, in which, the pyrazole fragments prevent a Michael addition with thiol nucleophile.…”

“…Experimental and computational studies on curcumin structure demonstrated that the aromatic ring/substituents on it and β-diketone moieties are crucial for biological responses and kinetic stability. [1][2][3][4][5][6][7][8][9][10][11][12] Several synthetic curcumin analogues have been developed through chemical modifications on its pharmacophores such as pyrazole, [6,[13][14][15][16][17][18][19][20] 1,4-thiazepane, [7] monocarbonyl, [8] aza-aromatic, [9] N-alkyl β-enaminone curcuminoids. [10][11][12] to circumvent the limitations of curcumin.…”

“…Replacing the β-diketone by pyrazole ring may increase anticancer activities, [6,[13][14][15][16][17] water solubility and delay degradation of curcumin. [6,15,16,[18][19][20] In order to prepare pyrazole-modified analogues of curcumin, the amount of curcumin substrate needs to be large enough for semi-synthetic processes. However, the isolation of natural curcumin from the Curcuma longa rhizome is a costly and timeconsuming procedure.…”