Hydroxypyrone derivatives in drug discovery: from chelation therapy to rational design of metalloenzyme inhibitors

Arshad, Jahanzaib; Hanif, Muhammad

doi:10.1039/d2md00175f

Cited by 4 publications

(2 citation statements)

References 174 publications

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“…These heterocycles demonstrate a multifarious reactivity that made them convenient building blocks for the organic synthesis of complex molecules via various transformations, , including cycloadditions and ring-opening transformations . Also, it is important to note that hydroxylated 4-pyrones are widely used as chelating agents and fluorescent labels …”

Section: Introductionmentioning

confidence: 99%

Oxidative Ring-Opening Transformation of 5-Acyl-4-pyrones as an Approach for the Tunable Synthesis of Hydroxylated Pyrones and Furans

Steparuk,

Meshcheryakova,

Viktorova

et al. 2023

J. Org. Chem.

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A selective and tunable approach for oxidation of 4-pyrones has been developed via ring-opening transformations leading to various hydroxylated oxaheterocycles. The first step of the strategy includes the base-catalyzed epoxidation of 5-acyl-4-pyrones in the presence of hydrogen peroxide for the effective synthesis of pyrone epoxides in high yields. The epoxides bearing the CO2Et group are reactive molecules that can undergo both pyrone and oxirane ring-opening via deformylation to produce hydroxylated 2-pyrones or 4-pyrones. The acid-promoted transformation led to 3-hydroxy-4-pyrones (24–76% yields), whereas the K2CO3-catalyzed ring-opening process of 2-carbethoxy-4-pyrone epoxides proceeded as an attack of alcohol at the C-3 position bearing the CO2Et group to give functionalized 6-acyl-5-hydroxy-2-pyrones (27–87% yields). The base-catalyzed reaction of 2-aryl-4-pyrone epoxides was followed by ring contraction and the dearoylation process to produce 3-hydroxyfuran-2-carbaldehydes in 42–80% yields. The transformation of 3-aroylchromone epoxides led to flavonols and 3-hydroxybenzofuran-2-carbaldehyde in the acidic and basic conditions, respectively. The prepared hydroxylated heterocycles demonstrated high reactivity for further transformations and low cytotoxicity and are promising fluorophores or UV filters.

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Section: Introductionmentioning

confidence: 99%

Oxidative Ring-Opening Transformation of 5-Acyl-4-pyrones as an Approach for the Tunable Synthesis of Hydroxylated Pyrones and Furans

Steparuk,

Meshcheryakova,

Viktorova

et al. 2023

J. Org. Chem.

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“…Among the recent reviews, Arshada and Hanif surveyed the chelating effects of some natural products, i.e., hydroxypyridone and hydroxythiopyridone derivatives, against several metalloenzymes implicated in cancer, diabetes and microbial diseases, including histone deacetylase (HDAC), tyrosinase and MBL. 21 However, several other small-molecule scaffolds with more potent activities against specifically MBLs were overlooked. Canton and co-workers also reviewed the resistance mechanisms of Pseudomonas aeruginosa and promoted the potency of siderophore cephalosporin cefiderocol as a treatment option in clinical conditions based on previous preclinical investigations.…”

Section: Introduction To Antimicrobial Resistance (Ar)mentioning

confidence: 99%

Small-molecule inhibitors of bacterial-producing metallo-β-lactamases: insights into their resistance mechanisms and biochemical analyses of their activities

2023

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Beyond cisplatin: New frontiers in metallodrugs for hard-to-treat triple negative breast cancer

Muhammad,

Hanif,

Yang

2024

Coordination Chemistry Reviews

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Hydroxypyrone derivatives in drug discovery: from chelation therapy to rational design of metalloenzyme inhibitors

Abstract: The versatile structural motif of hydroxypyrone is found in natural products and can be easily converted into hydroxypyridone (HOPO) and hydroxythiopyridone (THOPO) analogues. The favourable toxicity profile and ease of...

Cited by 4 publications

References 174 publications

Oxidative Ring-Opening Transformation of 5-Acyl-4-pyrones as an Approach for the Tunable Synthesis of Hydroxylated Pyrones and Furans

Oxidative Ring-Opening Transformation of 5-Acyl-4-pyrones as an Approach for the Tunable Synthesis of Hydroxylated Pyrones and Furans

Small-molecule inhibitors of bacterial-producing metallo-β-lactamases: insights into their resistance mechanisms and biochemical analyses of their activities

Beyond cisplatin: New frontiers in metallodrugs for hard-to-treat triple negative breast cancer

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