Synthetic method of methylene ether urushiol hydroxamic acid derivatives with (histone deacetylase) HDAC inhibitory activity

Abstract

The invention relates to a synthetic method of methylene ether urushiol hydroxamic acid derivatives with (histone deacetylase) HDAC inhibitory activity. Unsaturated urushiol is taken as a raw material, and oxidative polymerization of the urushiol is blocked through an etherification reaction; hydroxamic acid groups are introduced to tail parts of side chains of the urushiol thorugh a Diels-Alder reaction, a hydrolysis reactions, a hydroxylation reaction and the like; and in addition, different pharmacological groups such as nitro groups, hydroxyl groups and the like are introduced into benzene rings or alkyl chains, so that three methylene ether urushiol hydroxamic acid derivatives are synthesized. The three compounds can be well combined with active pockets of HDAC, can form stable hydrogen bonds with residual groups of the HDAC for interaction, and can be stably chelated with Zn<2+> at the bottom of the active pockets, so that good HDAC inhibitory activity is achieved. The median inhibitory concentrations (IC50) of the three compounds on HDAC 2 and HDAC 8 are equivalent to the IC50 value of an HDAC inhibitor SAHA approved by the Food and Drug Administration (FDA). The three compounds can be applied to clinical antitumor drugs and have extremely high additional values, and the synthetic method can be a novel technology for clinically developing novel phenol-based HDAC inhibitors.

Description

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AI Technical Summary

Benefits of technology

This patented method involves making small amounts (one millionth or less) of naturally occurring urushimene by extracting it from plants called LacerTree through various methods such as solvent extraction techniques like liquid/liquid separation, filtration, centrifugations, precipitation, etc., followed by purification steps for obtaining specific compounds containing this molecule's chemical formula. These new types are useful agents against cancer because they have strong cytotoxic properties but also show promise due their potential use as an effective treatment option on other diseases caused by abnormal cell growth.

Problems solved by technology

This patented technical problem addressed in this patents relates to developing novel nonsteroidal chemotherapy agents called uruimers due to poor water solubility properties and instability under physically demanding conditions. These drawbacks make these therapies difficult to use safely because they may cause harmful side effectings like cardiotoxicity when administered alone. Chemoattractants play a role in prevention against various diseases including breast cancer and lung cancer. Unlike other substances known herbals, urupiside A exhibits unique features from being able to bind strongly to DNA without affecting normal functions associated with protein metabolism. Its molecular formula describes three classes of ubiquitous carboxylic esters containing five sulfur atoms linked together.

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