Synthesis and Biological Evaluation of Kojic Acid Derivatives Containing 1,2,4‐triazole as Potent Tyrosinase Inhibitors

Abstract

A series of 5-substituted-3-[5-hydroxy-4-pyrone-2-yl-methymercapto]-4-amino-1,2,4-triazole derivatives were synthesized by nucleophilic substitution reaction of 5-hydroxy-2-chloromethyl -4H-pyran-4-one with 5-substituted-3-mercapto-4-amino-1,2,4-triazole, and their inhibitory effects on mushroom tyrosinase were evaluated. The results indicated that most of the synthesized compounds exhibited significant inhibitory activity. Specifically, 5-(4-chlorophenyl)-3-[5-hydroxy-4-pyrone-2-yl-methymercapto]-4-amino-1,2,4-triazole (6j) exhibited the most potent tyrosinase inhibitory activity with IC50 value of 4.50 ± 0.34 μm. The kinetic studies of the compound (6j) demonstrated that the inhibitory effects of the compound on the tyrosinase were belonging to competitive inhibitors. Meanwhile, the structure-activity relationship was also discussed.

Synthesis of New Benzimidazole‐1,2,3‐triazole Hybrids as Tyrosinase Inhibitors

“…Moreover, it has been described that 1,2‐3‐triazole‐containing analogs of the naturally occurring cyclo[Pro‐Val‐Pro‐Tyr] (such as C ) were effective tyrosinase inhibitors (IC 50 = 0.5 m m ) . It has been also reported that the kojic acid derivative containing 1,2,4‐triazole ( D ) exhibited better tyrosinase inhibitor activity (IC 50 = 4.50 μ m ) than kojic acid (IC 50 = 19.00 μ m ) . Considering these structural features and principles of bioisoterism, we designed a series of tyroinase inhibitors by employing fragment‐based drug design strategy.…”

Synthesis and research of the physical-chemical properties of 5-((2-bromphenyl)-4-amino-4H-1,2,4-triazole-3-ylthio)acetic acid salts

“…Як вихідні речовини обрали 2-бромбензойну кислоту, з якої через низку послідовних стадій отримали 5-(2-бром-феніл)-4-аміно-4Н-1,2,4-тріазол-3-тіон [10][11][12].…”

“…Для аналізу солі очищені перекристалізацією із суміші вода:ацетон (1:3). (8,9,11). До 0,01 моль 2-(5-(2-бром-феніл)-4-аміно-4Н-1,2,4-тріазол-3-ілтіо)ацетатної кислоти у 30 мл і-пропанолу додають 0,01 моль піпе-ридину (8), морфоліну (9) або піперазину (11) і нагрі-вають до розчинення.…”

“…Для аналізу сполуки перекристалізовані з ацетону. (11). До 0,01 моль відповідної 2-(5-(2-бромфеніл)-4-аміно-4Н-1,2,4-трі-азол-3-ілтіо)ацетатної кислоти додають 50 мл 25 % розчину амоніаку та перемішують до розчинення.…”

Synthesis and Biological Evaluation of S-Substituted Perhalo-2-nitrobuta-1,3-dienes as Novel Xanthine Oxidase, Tyrosinase, Elastase, and Neuraminidase Inhibitors

“…This enzyme is widely distributed in plants, microorganisms, fungi, and animals [36]. Tyrosinase is also responsible for the production of neuromelanin.…”