@conference{
author = "Videnović, Milica and Srdić-Rajić, Tatjana and Opsenica, Igor and Radulović, Siniša and Šolaja, Bogdan A.",
year = "2016",
abstract = "Background
Cancer is the second leading cause of morbidity and mortality worldwide, with approximately 14 million
new cases and 8.2 million cancer-related deaths in 2012.1
Current chemotherapy targets the proliferative
advantage of tumor cells over healthy cells, but the lack of selectivity of chemotherapeutic agents usually
leads to serious side effects. A major challenge in the development of effective and safe cancer treatment
is to identify the agents that could affect cellular processes essential for, or greatly enhanced in, malignant
cells only.
Aims
Benzothiazole derivatives represent a series of compounds of an undoubted interest because of the broad
spectrum of biological effects associated with this scaffold.2
In addition, benzothiazoles have attracted
considerable attention in anticancer research and a lot of structural modifications on their core nuclei have
been made to improve the antitumor activity. Therefore, we have synthesized novel benzothiazolamine
derivatives and investigated their anticancer potential against MCF-7 human breast cancer cell line.
Methods
We have synthesized a series of novel benzothiazolamine carbamates and amides starting from 1-chloro4-nitrobenzene and an appropriate alkylthiol, 3 followed by cyclization to benzothiazolamine and further
derivatization of amino-group. The selected compounds were subjected to a panel of NCI-60 cell line for
in vitro determination of antitumor activity. For better insight into possible mechanism of antiproliferative
activity, we have examined the cell cycle phase distribution and apoptosis in MCF-7 human breast cancer
cell line using flow cytometry methods, after treatment with synthesized compounds. Our research
continued towards examination of our compounds’ influence on the reactive oxygen species level,
mitochondrial membrane potential, as well as cell cycle regulators.
Results
The cell cycle phase distribution and apoptosis in MCF-7 human breast cancer cell line were investigated
after exposure to IC50 concentrations, obtained in vitro, of four selected compounds (Figure 1.b) for 24
and 48 hours, respectively. Using flow cytometry after PI staining we showed that our compounds affect cell cycle distribution in a
time dependent manner. After 24 h treatment, the portion of cells in G2/M phase increased, suggesting
cell cycle arrest in mitosis. After 48 hours, the number of sub G1 phase cells increased, which indicates
apoptosis.
Following incubation with selected compounds for 48 hours, the proapoptotic effect was reflected by the
increase of portion of early apoptotic cells up to 63 % measured by bivariate Annexin V/PI flow
cytometry (Figure 1.a). Moreover, we observed the loss of mitochondrial membrane potential, which
could indicate that our compounds promote apoptosis via the mitochondrial pathway in MCF-7 cells. In
addition, reactive oxygen species level in MCF-7 cells significantly decreased after treatment with
benzothiazolamine derivatives.
Conclusion
Benzothiazolamine carbamates and amides showed great potency for promoting highly specific
programmed cell death apoptosis in MCF-7 cancer cell line. Further examination will eventually provide
identification of molecular targets of benzothiazolamines. Our data offer a significant contribution to the
search for medicinally active compounds and may lead to discovery of a new potent antitumor agent.",
journal = "European School of Medicinal Chemistry (XXXVI Advanced Course of Medicinal Chemistry and "E. Duranti" National Seminar for PhD Students) Proceedings of PhD student poster session",
title = "New benzothiazolamine derivatives as inducers of an early apoptosis in MCF-7 human breast cancer cell line",
pages = "75-76",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5349"
}
