Synthesis & evaluation of some anti-proliferative substances

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Kang, Y., 2003. Synthesis & evaluation of some anti-proliferative substances. PhD, Nottingham Trent University.

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Abstract

In previous patented investigations at The Nottingham Trent University, it was found that a number of compounds with the general structure ArO(CH2)nNR1R2 presented significant fungicidal potency. With sponsorship from the British Technology Group, the most promising compounds of the series were prepared in gram quantities, using established or improved methods, and were subjected to in vitro and in vivo toxicity testing. Some were confirmed as being potent against Aspergillus species in vitro and relatively non-toxic but none was active in vivo.

The major part of the investigation was the synthesis of analogues of an aminoalkyloxybromobenzofuran, RWA2109, prepared by a previous student, which had shown remarkable activity in an anti-invasion screen operated by Professor S. Mac Neil's group at Sheffield University.

A number of structural isomers of RWA2109 were synthesized, and attempts were made to resolve an ambiguity in the structure of the parent compound. A water-soluble sulfoxide analogue, KY30a, was also prepared. The study was extended by the preparation of compounds in which the benzofuran nucleus was replaced by an indole or N-alkyl indole.

Considerable efforts were made to replicate the early anti-invasion results obtained with RWA2109, using of necessity a complex and laborious technique. It became obvious that the melanoma cell line originally used no longer gave reproducible results even as control, and was replaced by a more robust line, again with disappointing results.

It was however established that some of the indoles synthesized, and KY30a were potent in an anti-proliferation assay, with IC50 values of less than 5μM. There was also some indication that these compounds were active at very low concentration in the anti-invasion assay, but this result has to be regarded with caution.

Item Type:

Thesis

Creators:

Kang, Y.

Date:

2003

ISBN:

9781369325003

Identifiers: