TY - JOUR
T1 - Photo-induced cytotoxicity of prodigiosin analogues
AU - Park, Gyungse
AU - Tomlinson, John T.
AU - Misenheimer, Jacob A.
AU - Kucera, Gregory L.
AU - Manderville, Richard A.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2007/1
Y1 - 2007/1
N2 - Prodigiosin (1) is the parent member of a class of polypyrrole natural products that exhibit promising anticancer activities. They can facilitate copper-promoted oxidative DNA damage by binding to copper ions, and this activity is thought to represent their mechanism of cytotoxicity in the dark. They also possess photoinduced cytotoxicity, although 1 is too toxic in the dark to be used effectively for the treatment of cancer by photodynamic therapies. To circumvent dark toxicity by prodigiosins, the semi-synthetic analogue 2, in which the N-pyrrolic atoms of 1 are methylated to block copper coordination, and the synthetic phenyl analogues 3 and 4, which lack the copper-coordinating A-pyrrole ring of 1, were tested for their ability to inhibit colony formation of HL-60 cancer cells in the absence and presence of visible light (λ > 495 nm). Our results show that 2-4 lack cytotoxicity in the dark, but are able to inhibit colony formation of HL-60 cells following irradiation for 30 min. The synthetic derivative 4 exhibits photo-induced cytotoxicity similar to that of the natural product 1, demonstrating the potential use of prodigiosin-based compounds for treatment of cancers following irradiation with visible light.
AB - Prodigiosin (1) is the parent member of a class of polypyrrole natural products that exhibit promising anticancer activities. They can facilitate copper-promoted oxidative DNA damage by binding to copper ions, and this activity is thought to represent their mechanism of cytotoxicity in the dark. They also possess photoinduced cytotoxicity, although 1 is too toxic in the dark to be used effectively for the treatment of cancer by photodynamic therapies. To circumvent dark toxicity by prodigiosins, the semi-synthetic analogue 2, in which the N-pyrrolic atoms of 1 are methylated to block copper coordination, and the synthetic phenyl analogues 3 and 4, which lack the copper-coordinating A-pyrrole ring of 1, were tested for their ability to inhibit colony formation of HL-60 cancer cells in the absence and presence of visible light (λ > 495 nm). Our results show that 2-4 lack cytotoxicity in the dark, but are able to inhibit colony formation of HL-60 cells following irradiation for 30 min. The synthetic derivative 4 exhibits photo-induced cytotoxicity similar to that of the natural product 1, demonstrating the potential use of prodigiosin-based compounds for treatment of cancers following irradiation with visible light.
KW - Cancer treatment
KW - Cytotoxicity
KW - Photophysical property
KW - Prodigiosin
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U2 - 10.5012/bkcs.2007.28.1.049
DO - 10.5012/bkcs.2007.28.1.049
M3 - Article
AN - SCOPUS:33846480409
SN - 0253-2964
VL - 28
SP - 49
EP - 52
JO - Bulletin of the Korean Chemical Society
JF - Bulletin of the Korean Chemical Society
IS - 1
ER -