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Alkylated pyridyl amphiphiles display a pro‐apoptotic profile in cancerous cell lines dependent on hydrophobic chain length
Author(s) -
CarrilloAlvarado Miguel Angel,
Hernandez Evelyn Angel,
Pardo Andrew Angel,
VarelaRamirez Armando Angel,
Noveron Juan Angel
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.836.19
Subject(s) - pyridinium , cytotoxicity , apoptosis , chemistry , amphiphile , alkyl , hela , phosphatidylserine , cationic polymerization , cancer cell , cell culture , cell cycle , stereochemistry , cell , biochemistry , cancer , biology , medicinal chemistry , organic chemistry , phospholipid , membrane , in vitro , copolymer , polymer , genetics
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 CC 50 '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 Information The 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 .