Alkyl ether analogs of chlorophyll-a derivatives: Part 1. Synthesis, photophysical properties and photodynamic efficacy.
The synthesis, preliminary in vivo biological activity, singlet oxygen and fluorescence yields of a series of alkyl ether derivatives of chlorophyll-alpha analogs are described. For short-chain carbon ethers (1-7 carbon units), it was observed that the biological activity increased by increasing the length of the carbon chain, being maximum in compounds with n-hexyl and n-heptyl chains. Related sensitizers prepared by reacting 2-(1-bromoethyl)-2-devinylpyropheophorbide-alpha with (sec)alcohols were found to be less effective. Under similar treatment conditions, photosensitizers containing cis- and trans- 3-hexenyl side chains were ineffective. Thus, both stereochemical and steric factors caused differences in sensitizing activity. In general, pyropheophorbide-alpha analogs were found to be more active than related chlorin e6 derivatives, in which the isocyclic ring (ring "E") was cleaved. Related photosensitizers in the 9-deoxy- series were found to be as effective as the corresponding pyropheophorbide-alpha analogs. The photosensitizers prepared from pyropheophorbide-alpha methyl ester and chlorin e6 trimethyl ester have long wavelength absorption at 660 nm (epsilon 45 000 to 50 000). Reduction of the carbonyl group in the pyropheophorbide-alpha to methylene (ring E) resulted in a blue shift to 648 nm (epsilon 38 000).
Pandey
R K
RK
Department of Radiation Biology, Roswell Park Cancer Institute, Buffalo, NY 14263-0001, USA.
Sumlin
A B
AB
Constantine
S
S
Aoudla
M
M
Potter
W R
WR
Bellnier
D A
DA
Henderson
B W
BW
Rodgers
M A
MA
Smith
K M
KM
Dougherty
T J
TJ
D000818:Animals; D002734:Chlorophyll / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000077194:Chlorophyll A; D051379:Mice; D008811:Mice, Inbred DBA; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010777:Photochemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D017319:Photosensitizing Agents; D002734:Chlorophyll; D000077194:Chlorophyll A