Abstract:
This PhD thesis is the result of work performed in the laboratory of Dr. Naibedya
Chattopadhyay in the Division of Endocrinology, CSIR-Central Drug Research
Institute, Lucknow, during the period 2007-2011. My fellowship, Ph.D.-fee and an
annum was funded by the Council of Scientific and Industrial Research, New Delhi.
The fundamental aim of this dissertation was discovery of small molecule inhibitors
that are orally active against growth factor receptors to stall the growth of breast
cancer. To that effect, two novel synthetic series, phenyl naphthalen-1-yl methanone
oxime derivatives and benzoxazepine derivatives were studied. The results of this
study have been presented in three chapters for better correlation of the data.
Chapter 1
We evaluated the anti-proliferative effect of novel phenyl naphthalen-1-yl methanone
oxime derivatives in human breast cancer cells. Subsequently, we have determined
the effect of most active compound of the series, 6b on the induction of apoptosis of
breast cancer cells, regression of xenograft tumor and its molecular target.
Chapter 2
We investigated the anti-tumor activity of a new series of benzoxazepine derivatives
in breast cancer. We then identified the most potent compound of the series, 4-[4-
(Toluene-4-sulfonyl)-2, 3, 4, 5-tetrahydro-benzo[f] [1, 4] oxazepin-3-ylmethyl]-
phenol (THBP), studied its effect on the induction of apoptosis of human breast
cancer cells, regression of xenograft tumor and determined its molecular target.
Chapter 3
We investigated the combinatorial effect of EGFR and IGF-1R inhibition by 6b and
THBP on human breast cancer cells.
