Affiliations: Department of Biological Sciences, Purdue University,
West Lafayette, IN 47907, USA | Department of Human Ecology, University of Texas,
Austin, TX 78712, USA
Note: [] Address for correspondence: Richard Willis, Department of Human
Ecology, University of Texas, Austin, TX 78712, USA. E-mail:
[email protected]
Abstract: This study was organized by Professor Karl Folkers with the
objective of finding derivatives of coenzyme Q which could be more effectively
absorbed and would give better biomedical effects. In this series all the
compounds are 2,3 dimethoxy, 5 methyl p benzoquinone with modified side chains
in the 6 position. The modifications are primarily changes in chain length,
unsaturation, methyl groups and addition of terminal phenyl groups. The test
system evaluates the growth of serum deficient HL60, 3T3 and HeLa cells in the
presence of coenzyme Q_{10} or coenzyme Q analogs. Short
chain coenzyme Q homologues such as coenzyme Q_2 give poor
growth but compounds with saturated short aliphatic side chains from C10 to C18
produce good growth. Introduction of a single double bond at the 2' or 8'
position in the aliphatic chain retains growth stimulation at low concentration
but introduces inhibition at higher concentration. Introduction of a 3' methyl
group in addition to the 2' enyl site in the side chain decreases the growth
response and maintains inhibition. Addition of a terminal phenyl group to the
side chain from C5 to C10 can produce analogs which give strong stimulation or
strong inhibition of growth. The action of the analogs is in addition to the
natural coenzyme Q in the cell and is not based on restoration of activity
after depletion of normal coenzyme Q. The effects may be based on any of the
sites in the cell where coenzyme Q functions. For example, coenzyme
Q_2 is known to decrease mitochondrial membrane potential
whereas the analog with a 10C aliphatic side chain increases potential. Both of
these compounds stimulate plasma membrane electron transport. Inhibition of
apoptosis by coenzyme Q may also increase net cell proliferation and the 10C
analog inhibits the permeability transition pore.
Keywords: coenzyme Q analogs, cell growth
Journal: BioFactors, vol. 18, no. 1-4, pp. 307-314, 2003
