Rational Design, Synthesis, in Vitro, and in Silico Studies of Chlorophenylquinazolin‐4(3H)‐One Containing Different Aryl Acetohydrazides as Tyrosinase Inhibitors

Abstract

Tyrosinase plays a pivotal role in the hyperpigmentation and enzymatic browning of fruit and vegetable. Therefore, tyrosinase inhibitors can be of interest in industries as depigmentation compounds as well as anti‐browning agents. In the present study, a series of chlorophenylquinazolin‐4(3H)‐one derivative were rationally designed and synthesized. The formation of target compounds was confirmed by spectral characterization techniques such as IR, 1H‐NMR, 13C‐NMR, and elemental analysis. Among the synthesized derivatives, compound 8l was proved to be the most potent inhibitor with an IC50 value of 25.48±1.19 μM. Furthermore, the results of the molecular docking study showed that this compound fitted well in the active site of tyrosinase with the binding score of −10.72.

Heterocyclic Compounds as Synthetic Tyrosinase Inhibitors: Recent Advances

“…Iraji and co-workers designed and synthesized a series of chlorophenylquinazolin-4(3H)-one derivatives (84, Figure 54) containing various aryl acetohydrazides as potential TYRIs [99]. The percentage of TYR inhibition resulted between 63.48 and 1.02%.…”

Synthesis of 3-hydroxypyridin-4-one derivatives bearing benzyl hydrazide substitutions towards anti-tyrosinase and free radical scavenging activities

“…4 So far, several natural and synthetic inhibitors for tyrosinase enzymes have been identied. [5][6][7][8] The studies showed that the compounds can inhibit tyrosinase enzyme in several different ways, including reduction of dopaquinone to dopa (ascorbic acid), 9 reduction of the amount of dopaquinone (thiol analogs), 10 and much greater affinity to tyrosinase enzyme compared to the main substrate (phenolic compounds). 11 Also, the alteration in the shape of the active site of the enzyme, such as compounds with acidic or basic properties, 12 the inactivation of the enzyme through the covalent bond with the enzyme, and irreversible inhibition of the enzyme, 13 and nally, the occupation of the active site and reversible inhibition of the enzyme 14 are the other mechanisms of tyrosinase inhibition.…”

Design, synthesis, in vitro, and in silico evaluations of kojic acid derivatives linked to amino pyridine moiety as potent tyrosinase inhibitors

“…Melanin produced by melanocytes is responsible for the pigmentation of skin, hair, and eyes and plays an important role in protecting human skin from the destructive effect of UV radiation and oxidative stress []. However, excessive melanin synthesis can cause abnormal pigmentation, age spots, freckles, and induce skin diseases as well as malignant melanoma [ 1 ]. Tyrosinase (EC 1.14.18.1, TYR) is metalloenzyme with six histidine residues and two conserved copper ions in its active site, which is essential for the catalytic activity of tyrosinase [ 2 ].…”