Rapid synthesis and zebrafish evaluation of a phenanthridine-based small molecule library.

نویسندگان

  • Lauren R Donaldson
  • Stephen Wallace
  • David Haigh
  • E Elizabeth Patton
  • Alison N Hulme
چکیده

A Heck cyclisation approach is described for the rapid synthesis of a library of natural product-like small molecules, based on the phenanthridine core. The synthesis of a range of substituted benzylamine building blocks and their incorporation into the library is reported, together with a highly selective cis-dihydroxylation protocol that enables access to the target compounds in an efficient manner. Biological evaluation of the library using zebrafish phenotyping has led to the discovery of compound 20c, a novel inhibitor of early-stage zebrafish embryo development.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The recent development in synthesis and pharmacological evaluation of small molecule to treat Alzheimer's diseases: A review

Alzheimer's disease is a neurological disorder in which the death of brain cells causes memory loss and cognitive decline. A neurodegenerative type of dementia, the disease starts mild and gets progressively worse. Like all types of dementia, Alzheimer's is caused by brain cell death. The most common presentation marking Alzheimer's dementia is where symptoms of memory loss are the most promine...

متن کامل

The recent development in synthesis and pharmacological evaluation of small molecule to treat Alzheimer's diseases: A review

Alzheimer's disease is a neurological disorder in which the death of brain cells causes memory loss and cognitive decline. A neurodegenerative type of dementia, the disease starts mild and gets progressively worse. Like all types of dementia, Alzheimer's is caused by brain cell death. The most common presentation marking Alzheimer's dementia is where symptoms of memory loss are the most promine...

متن کامل

Design, Synthesis and Evaluation of Substituted Aryl-2-Nitrovinyl Derivatives as Small Molecules Proteasome Inhibitors

Based on the existing structure activity relationship for proteasome inhibitors, a number of substituted aryl-2-nitrovinyl derivatives have been synthesized as Michael acceptor and their cytotoxicity and proteasome inhibitory effects were evaluated on two cancer cell lines. Compound 2d exhibited IC50 values of 0.71 and 17.79 μM comparable to bortezomib against MCF-7 and PC-3, respectively. The ...

متن کامل

Design, Synthesis and Evaluation of Substituted Aryl-2-Nitrovinyl Derivatives as Small Molecules Proteasome Inhibitors

Based on the existing structure activity relationship for proteasome inhibitors, a number of substituted aryl-2-nitrovinyl derivatives have been synthesized as Michael acceptor and their cytotoxicity and proteasome inhibitory effects were evaluated on two cancer cell lines. Compound 2d exhibited IC50 values of 0.71 and 17.79 μM comparable to bortezomib against MCF-7 and PC-3, respectively. The ...

متن کامل

Large scale zebrafish-based in vivo small molecule screen.

Given their small embryo size, rapid development, transparency, fecundity, and numerous molecular, morphological and physiological similarities to mammals, zebrafish has emerged as a powerful in vivo platform for phenotype-based drug screens and chemical genetic analysis. Here, we demonstrate a simple, practical method for large-scale screening of small molecules using zebrafish embryos.

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Organic & biomolecular chemistry

دوره 9 7  شماره 

صفحات  -

تاریخ انتشار 2011