SUPERIOR CHEMOTHERAPEUTIC AGENTS BY RATIONAL DESIGN

合理设计的优质化疗药物

• 批准号: 3284000
• 负责人: GARY A EPLING
• 金额: $ 4.86万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3284000
• 关键词: antimalarial agents; chemical structure function; cytotoxicity; drug adverse effect; drug design /synthesis /production; drug screening /evaluation; nonvisual photosensitivity; skin neoplasms; vision disorders; vitiligo

Ingestion of many naturally-occurring compounds, as well as many synthetic drugs, produces "phototoxicity" in humans and animals, so that subsequent exposure to light causes skin or vision damage, or induction or acceleration of cancer. To synthetically modify these drugs to avoid this side effect is a difficult task because of uncertainty about the molecular and mechanistic basis for this undesired photobiological activity, so there have been very few suggestions of possible approaches which might be successful in overcoming this inherent tendency towards phototoxicity in a drug. This proposal describes three mechanistically-derived approaches to the rational synthesis of new chemotherapeutic agents of dramatically lessened phototoxicity. These approaches will be tested in the synthesis of new compounds expected to exhibit high antimalarial activity, yet be non-phototoxic. Success with these compounds will not only result in new antimalarial compounds which are desperately needed,but will also demonstrate the validity of a mechanistically-derived approach to solving the problem of phototoxicity in other dissimilar classes of compounds which also suffer from this side effect.

摄取许多自然产生的化合物，以及许多合成的 药物，在人类和动物身上产生“光毒性”，因此随后 暴露在光线下会导致皮肤或视力损害，或感应或 癌症的加速。对这些药物进行综合修饰以避免这种情况 副作用是一项困难的任务，因为关于分子的不确定性 以及这种不受欢迎的光生物活动的机制基础，所以 几乎没有关于可能的方法的建议 成功地克服了这种固有的光毒性倾向 毒品。本提案描述了三种机械派生的方法，以 新型抗癌化疗药物的合理合成 降低了光毒性。这些方法将在合成中进行测试 有望显示出高抗疟疾活性的新化合物，但 无光毒性。这些化合物的成功不仅会带来新的 迫切需要的抗疟疾化合物，但也会 证明机械派生方法解决问题的有效性 其他不同类别的化合物的光毒性问题 也会受到这种副作用的影响。