Synthesis of bioreductive esters from fungal compounds.
Four new bioreductive esters (7-10) have been synthesized. Their structures composed of trimethyl lock containing quinone propionic acid with an ester linkage to the fungal cytotoxic compounds; preussomerin G (1), preussomerin I (2), phaseolinone (3) and phomenone (4). The synthesized esters are aimed to act via reductive activation specifically at the cancer cells, resulting from hypoxia and overexpression of reductases. Hence, the toxicity will be lessened during distribution across the normal cells. The anticancer activity was determined in cancer cell lines with reported reductase i.e., BC-1 cells and NCI-H187 as well as in non-reductase containing cancer cells; KB cells. When considering each cell lines, result showed that structure modification giving to 7-10 led to less cytotoxicity than their parent compounds (1-4). Both 7 and 8 were strongly cytotoxic (IC50 < or = 5 microg/ml) to NCI-H187, whereas 9 and 10 were moderately cytotoxic (IC50 = 6-10 microg/ml) to BC-1 cells. Additional study of stability of represented phenolic ester (8) and an alcoholic ester (9) were performed. Result illustrated that both 8 and 9 were stable in the presence of esterase. Therefore, the cytotoxicity of the synthesized compounds (8-10) might be due to partial bioreductive activation in the cancer cells.
Weerapreeyakul
Natthida
N
Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand. natthida@kku.ac.th
Anorach
Rutchayaporn
R
Khuansawad
Thidarut
T
Yenjai
Chavi
C
Isaka
Masahiko
M
D045744:Cell Line, Tumor; D004952:Esters / Q000138:chemical synthesis*; D005658:Fungi / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared
D004952:Esters