Identification and the characterization of small molecules with potential anticancer activity against solid tumors
Author
Durmaz, İrem
Advisor
Çetin-Atalay, Rengül
Date
2011Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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Abstract
The ultimate goal of our project was to investigate candiate small molecules
with a potential anticancer activity and characterize their mode of action.
Cardiac glycosides are important group of molecules for both their treating
properties in heart failure and their potential effects in cancer therapy. We
investigated the cardiac glycosides that are extracted from Digitalis Ferruginea
which can be frequently found in Turkey. These glycosides are Lanatoside A,
Lanatoside C and Glucogitorosid. Our results showed that they constitute high
cytotoxicity effect against liver cancer cell lines. In addition they cause G2/M cell
cycle arrest and thereby induce apoptosis.
For the synthetic molecules, we first tested a set of molecules that are
synthesized as derivatives of kinase inhibitors. There are some commercial drugs
such as imatinib or erlotinib that are used frequently for cancer treatment. Thus we
wanted to investigate if these molecules comprise cytotoxic activities. Our data
revealed that especially one of the molecules out of 16 display high cytotoxicity and
high kinase inhibitory effect in liver cancer cell lines.
The final group of molecules we tested was compoused of thiazolidine ring.
In this group of molecules, only one molecule, the one with alkyne terminal
precursor, caused cytotoxicity against cancer cell lines. Besides, we have shown that
it induces SubG1/G1 cell cycle arrest in cancer cell lines.