2018英特尔ISEF获奖作品摘要 化学 Intel Finalist Abstract Chemistry

获奖作品基本信息

年份	2018
学科	化学 Chemistry
国家/州	United States of America

获奖作品名称

Cutting off Cancer: Design, Analysis, and Synthesis of Novel Vascular Disrupting Agents

获奖作品摘要

Cancer remains a pervasive and ominous threat as the second leading cause of death in the United States, accounting for one in four fatalities.  The survival and proliferation of tumors in cancer patients requires a vascular network to provide sufficient nutrients and oxygen to tumor cells. Recent research has focused on developing Vascular Disrupting Agents (VDAs) to selectively destroy tumor vasculature and initiate secondary tumor cell death. Combretastatin-A-4 (CA-4), a tubulin-binding agent, has reported preclinical successes as a VDA and set the precedent for further exploration. However, only one of CA-4’s geometric isomers has anti-cancer properties and previously synthesized analogs have failed to match its activity. This study aims to discover VDAs with improved efficacy and selective toxicity. While previous research has tended to analyze analogs of only one scaffold/model structure at a time, in this study many completely new molecular scaffolds were rationally designed and a library of 210 compounds based on analogs of these novel scaffolds was created. Following computational modelling and analysis, SB-BC-160, an analog of an original scaffold design, emerged as the most promising compound demonstrating geometric stability, desired hydrogen bonding, and ten-fold improved binding affinity to tubulin. A synthetic scheme for SB-BC-160 was created. When fully synthesized, SB-BC-160 will be biologically evaluated and serve as the basis to a new class of more potent, structurally stable VDAs, opening up new treatment options for the millions affected by cancer.

 

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ISEF 简介

英特尔国际科学与工程大奖赛，简称 "ISEF"，由美国 Society for Science and the Public（科学和公共服务协会）主办，英特尔公司冠名赞助，是全球规模最大、等级最高的中学生的科研科创赛事。ISEF 的学术活动学科包括了所有数学、自然科学、工程的全部领域和部分社会科学。ISEF 素有全球青少年科学学术活动的“世界杯”之美誉，旨在鼓励学生团队协作，开拓创新，长期专一深入地研究自己感兴趣的课题。

学科简介：化学 Chemistry

Studies exploring the science of the composition, structure, properties, and reactions of matter not involving biochemical systems.

Subcategories:

Analytical Chemistry (ANC): The study of the separation, identification, and quantification of the chemical components of materials.

Computational Chemistry (COM): A study that applies the discipline and techniques of computer science and mathematics to solve large and complex problems in Chemistry.

Environmental Chemistry (ENV): The study of chemical species in the natural environment, including the effects of human activities, such as the design of products and processes that reduce or eliminate the use or generation of hazardous substances.

Inorganic Chemistry (INO): The study of the properties and reactions of inorganic and organometallic compounds.

Materials Chemistry (MAT): The chemical study of the design, synthesis and properties of substances, including condensed phases (solids, liquids, polymers) and interfaces, with a useful or potentially useful function, such as catalysis or solar energy.

Organic Chemistry (ORG): The study of carbon-containing compounds, including hydrocarbons and their derivatives.

Physical Chemistry (PHC): The study of the fundamental physical basis of chemical systems and processes, including chemical kinetics, chemical thermodynamics, electrochemistry, photochemistry, spectroscopy, statistical mechanics and astro-chemistry.

Other (OTH): Studies that cannot be assigned to one of the above subcategories. If the project involves multiple subcategories, the principal subcategory should be chosen instead of Other.