In Vitro Preclinical Investigation of Novel Phenol, Indoline, and Morpholine Derivatives as Anticancer Agents
Doan, Bach Hai Phuong (2016)
Doan, Bach Hai Phuong
2016
Master's Degree Programme in Science and Bioengineering
Luonnontieteiden tiedekunta - Faculty of Natural Sciences
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Hyväksymispäivämäärä
2016-10-05
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tty-201609204524
https://urn.fi/URN:NBN:fi:tty-201609204524
Tiivistelmä
Phenolic compounds have received a considerable attention in anticancer field owing to their valuable therapeutic activity. In addition, indoline and morpholines have been considered as promising chemopreventive agents due to the higher efficiency in cancer therapy. This study aimed at exploiting sixteen alkylaminophenols, decorated with different secondary amines including indoline and morpholine as potential anticancer agents.
The results show that 2-((1,2,3,4-Tetrahydroquinolin-1-yl)(4-methoxyphenyl)methyl)phenol (2) and N-(2-Hydroxy-5-nitrophenyl(4’-methylphenyl)methyl)indoline (10) were found to exhibit strong inhibitory response against U2OS cells with the IC50 of ~ 51 µM and ~74 µM, respectively. Further studies indicated that such compounds are inhibitors of the metastatic property of tumor cells and induces cell death by apoptosis or necrosis. The ability of increasing ROS, inducing apoptosis, increasing mitochondrial calcium, and inducing caspases 3/7 were also generalized in U2OS and HEK293 cells. These results suggest an interlinking of higher level ROS with the cell death, a mitochondrial calcium-independent mechanism in triggering apoptosis and involvement of caspases pathway in apoptosis induction of treatment with 2 and 10.
This thesis demonstrates the potential anticancer properties of alkylaminophenols derived from indoline and tetrahydroquinoline. In perspective, the above mentioned results could be useful not only to select appropriate anticancer screening methods but also to develop future effective chemotherapy for cancer.
The results show that 2-((1,2,3,4-Tetrahydroquinolin-1-yl)(4-methoxyphenyl)methyl)phenol (2) and N-(2-Hydroxy-5-nitrophenyl(4’-methylphenyl)methyl)indoline (10) were found to exhibit strong inhibitory response against U2OS cells with the IC50 of ~ 51 µM and ~74 µM, respectively. Further studies indicated that such compounds are inhibitors of the metastatic property of tumor cells and induces cell death by apoptosis or necrosis. The ability of increasing ROS, inducing apoptosis, increasing mitochondrial calcium, and inducing caspases 3/7 were also generalized in U2OS and HEK293 cells. These results suggest an interlinking of higher level ROS with the cell death, a mitochondrial calcium-independent mechanism in triggering apoptosis and involvement of caspases pathway in apoptosis induction of treatment with 2 and 10.
This thesis demonstrates the potential anticancer properties of alkylaminophenols derived from indoline and tetrahydroquinoline. In perspective, the above mentioned results could be useful not only to select appropriate anticancer screening methods but also to develop future effective chemotherapy for cancer.