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Strategies toward Organic Carbon Monoxide Prodrugs
Accounts of Chemical Research ( IF 16.4 ) Pub Date : 2018-05-15 00:00:00 , DOI: 10.1021/acs.accounts.8b00019 Xingyue Ji 1 , Binghe Wang 1
Accounts of Chemical Research ( IF 16.4 ) Pub Date : 2018-05-15 00:00:00 , DOI: 10.1021/acs.accounts.8b00019 Xingyue Ji 1 , Binghe Wang 1
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Carbon monoxide is widely acknowledged as an important gasotransmitter in the mammalian system with importance on par with that of nitric oxide. It has also been firmly established as a potential therapeutic agent with a wide range of indications including organ transplantation, cancer, bacterial infection, and inflammation-related conditions such as colitis and sepsis. One major issue in developing CO based therapeutics is its delivery in a pharmaceutically acceptable form. Currently, there are generally five forms of deliveries: inhaled CO, photosensitive CO-releasing molecules, encapsulated CO, CO dissolved in drinks, and molecules that would release CO under physiological conditions without the need for light. For over a decade, the last category only included metal-based CO releasing molecules. What had been missing were organic CO prodrugs, which release CO under physiological conditions with tunable rates and in response to various exogenous and endogenous triggers such as water, chemical reagents, esterase, ROS, and changes in pH. This Account describes our work in this area as well as the demonstration for these organic prodrugs to recapitulate CO’s pharmacological effects both in vitro and in vivo.
中文翻译：
有机一氧化碳前药的策略
一氧化碳已被公认为是哺乳动物系统中的重要气体递质，其重要性与一氧化氮相当。它也已被牢固地确立为一种潜在的治疗剂，具有广泛的适应症，包括器官移植，癌症，细菌感染以及与炎症有关的疾病，例如结肠炎和败血症。开发基于CO的治疗剂的一个主要问题是其以药学上可接受的形式递送。当前，通常有五种递送形式：吸入的CO，释放光敏性的CO分子，包裹的CO，溶解在饮料中的CO以及在生理条件下无需光照即可释放CO的分子。十多年来，最后一个类别仅包括基于金属的CO释放分子。所缺少的是有机一氧化碳前药，在生理条件下以可调节的速率释放CO，并响应各种外源性和内源性触发因素，例如水，化学试剂，酯酶，ROS和pH值变化。该帐户描述了我们在该领域的工作以及这些有机前药的实例，以说明CO的药理作用体外和体内。
更新日期：2018-05-15
中文翻译：
有机一氧化碳前药的策略
一氧化碳已被公认为是哺乳动物系统中的重要气体递质，其重要性与一氧化氮相当。它也已被牢固地确立为一种潜在的治疗剂，具有广泛的适应症，包括器官移植，癌症，细菌感染以及与炎症有关的疾病，例如结肠炎和败血症。开发基于CO的治疗剂的一个主要问题是其以药学上可接受的形式递送。当前，通常有五种递送形式：吸入的CO，释放光敏性的CO分子，包裹的CO，溶解在饮料中的CO以及在生理条件下无需光照即可释放CO的分子。十多年来，最后一个类别仅包括基于金属的CO释放分子。所缺少的是有机一氧化碳前药，在生理条件下以可调节的速率释放CO，并响应各种外源性和内源性触发因素，例如水，化学试剂，酯酶，ROS和pH值变化。该帐户描述了我们在该领域的工作以及这些有机前药的实例，以说明CO的药理作用体外和体内。
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