(1104) Synthesis of Alpha Amino Acetamide Carbazole Derivative and Its Biological Evaluation in Cancer Cells

Objectives: Breast cancer remains among women's most diagnosed cancers worldwide, including in the United States and Puerto Rico. It is expected to have 297,790 newly diagnosed invasive breast cancer patients in women by 2023. Researchers have been focusing on carbazole derivatives as an alternative in cancer treatments. These compounds contain unique polycyclic, planar, and aromatic structures that allow them to contain pharmaceutical properties including antitumoral activity. Moreover, previous research has revealed the significant influences carbazole derivatives have on crucial processes such as cell cycle regulation, DNA repair, angiogenesis, and apoptotic pathways. Therefore, carbazole derivatives can offer effective therapeutic strategies against the progression of breast cancer cells. Our main goal is to design and synthesize new alpha amino acetamide carbazole derivatives and analyze their anti-cancer activity in the highly metastatic MDA-MB-231 breast cancer cell line.

Methods: Starting with aniline and 9-Ethyl- 3-carbazole carboxaldehyde in the presence of potassium cyanide, we used the Strecker synthesis method to prepare our carbazole derivatives. The biological evaluation of this carbazole derivative was done in vitro in MDA-MB-231 metastatic cells using Sulforhodamine B (SRB) assay protocol. The compounds were diluted at concentration ranging from 1.56 to 50 µM and incubated 37C for 48 h with the MDA-MB-231 cancer cells.

Results: The synthetic protocol affords an alpha amino acetamide carbazole derivative in 18% yield and after evaluation in MDA-MB-231 cells results demonstrated a mild cytotoxic effect after 48 h at varying concentrations. In addition, cell viability declined as the concentration increased. From the synthesis, compounds 3 and 4 showed a reduction in cell viability of MDA-MB-231 cells at 50 μM after 48 h with relative reduction in cell viability of 20% and 80%, respectively. Compound 4 demonstrated a GI50 = 19 μM on MDA-MB-231 cells.

Conclusions: Alpha amino acetamide carbazole derivative was demonstrated to have bioactivity against MDA-MB-231 cells at 50 μM. Furthermore, it may represent a possible anti-cancer agent in highly metastatic cells. However, further evaluation must be done to evaluate its effect as a possible anti-cancer agent such as the anti-migratory effect in MDA-MB-231 and other highly metastatic cancer cells. We acknowledge the project was supported by CAPAC (Award Grant Number # R25CA240120) from the NCI.