Abstract
Eleven 31-methylenlanostane triterpenoids, i.e., seven 21- and four 26-oic acids, as well as a lupane triterpenoid betulin, isolated from the fruiting bodies of the mushroom Fomitopsis betulina, were tested for in vitro protective effect on chromosome aberrations in peripheral human lymphocytes using cytochalasin-B blocked micronucleus (CBMN) assay. Most of the tested compounds showed a beneficial effect by reducing DNA damage of human lymphocytes more effectively than amifostine, a radioprotective agent, used as a positive control. All the tested compounds decreased MN frequency in the concentration dependent manner, with the concentration of 2.0 ?g mL-1 being the most effective ? with increase of the concentration the activity slightly decreases. The structure?activity relationship (SAR) studies indicated that the lanostanes containing a conjugated 7,9 (11)-diene system exhibit lower activity than ?8-analogues. It was also demonstrated that the DNA protective activities within the ?8-lanostane-26-oic acid group are affected by the substitution in position 3 pattern. In the ?8 series the oxygenation at C-12 or 16 as well as 21- or 26-oic acid functionality proved beneficial for in vitro protective effect on chromosomal aberrations. Betulin exhibited the lowest protective activity, but it is still comparable to that of amifostine.
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