Alkylated pyridyl amphiphiles display a pro‐apoptotic profile in cancerous cell lines dependent on hydrophobic chain length

Abstract

Cationic lipids, particularly those with nitrogen containing heterocycles, such as a pyridinium headgroup, display various bactericidal, bacteriostatic and disinfectant activity as reported in various works, all dependent on the length of their respective alkyl chains. Two quaternary alkyl pyridinium amphiphiles, vis. 4‐amino‐1‐decyl (1) and 4‐amino‐1‐dodecyl (2), were evaluated for their cytotoxic activity in a human cervical cancer cell line. These two compounds were assessed for their cytotoxicity and the following CC50's, 15.68 μM and 4.58 μM respectively were established. 1 proves to be a poor candidate as an anti‐cancer therapeutic agent as its cytotoxicity induced necrotic death. At a low concentration, 2 displayed a pro‐apoptotic profile demonstrated by phosphatidylserine externalization suggesting induction via an extrinsic pathway since it did not disrupt mitochondrial polarity. Of both compounds, 2, acts as a cell cycle progression disruptor causing slight S‐phase arrest and a decrease in G2/M phase along with eliciting DNA fragmentation. An explicit difference of two carbons between both 1 and 2 warrants further investigation to elucidate alkyl‐chain length role in anti‐cancer drugs. Furthermore, a series of these cationic amphiphiles with different lengths for their hydrophobic moiety has been synthesized and will be studied on a wider panel of cancer cell lines and have their mechanism of death further elucidated.Support or Funding InformationThe Cytometry, Screening and Imaging Core Facility that was used in this work was supported by the National Institute on Minority Health and Health Disparities (NIMHD) through a Research Centers for Minority Institutions (RCMI) grants 8G12MD007592 and 5G12MD007592, a component of the National Institutes of Health (NIH).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.