Design, synthesis and antitumor activities of chlorin p6 ether derivatives as photosensitizer for photodynamic therapy / 药学实践杂志

Objective To designe, synthesize a series of chlorin p6 ether photosensitizers and preliminarily investigate their photodynamic antitumor activity based on previous research results that alkoxyl ether derivatives of 3-vinyl on chlorin f exhibited stronger photosensitive antitumor activity than parent compound. Methods Purpurin-18 (4) was obtained by oxidative degradation with air and alkali on pheophorbide a (5) which was prepared through acid hydrolysis of chlorophyll a from crude chlorophyll extracts in Chinese traditional herb named Silkworm excrement. Then, chlorin p6 trimethylester (2) were formed via basic hydrolysis of internal anhydride ring for lead compound 3 and following immediately methylation with CH2N2. The intermediate 2 reacted with 33% HBr, following nucleophilic substitution with various alkoxyl alcohol to get six title compounds (1). All title compounds were subjected to photodynamic antitumor activity screening for melanoma B16-F10 cell in vitro. Results All title compounds showed much higher phototoxicity against melanoma B16-F10 cells than talaporfin and verteporfin. Their structures were confirmed by 1H-NMR, 13C-NMR, ESI-MS and ESI-HRMS spectra. Conclusion Chlorin p6 ether compounds were promising candidate photosensitizers for PDT applications due to theirs high dark toxicity/phototoxicity ratio and excellent phototoxicity, which were worthy of further research and development.

Design and synthesis of photosensitizer,13,15-cycloimides chlorin p6 / 药学实践杂志

Objective To design and prepare 13 ,15-cycloimides chlorin p6 (1) ,a class of chlorin related antitumor photo-sensitizers ,which contain a more stable six-membered cyclic imide comparing to the exocyclic anhydride ring of purpurin-18 (2) .Compounds (1) exhibit strong absorption at long wavelengths near λmax 700 nm to take full advantage of greater tissue penetration .Methods Pheophorbide a (3) was obtained by acid hydrolysis of chlorophyll a ,which was from crude chlorophyll extracts of Chinese traditional herb named Silkworm excrement .Purpurin-18 (2) was prepared by air oxidation and alkali open loop simultaneously on five-membered beta-keto carboxylic ester ring of pheophorbide a (3) .Finally ,the target compounds 1a~1j were synthesized via condensation of its anhydride ring with various amines including carboxyl-protected amino acids . Results Target compounds 1a~1j were successfully synthesized in yields ranged from 32 .6% to 65 .2% .Their structures were confirmed by elemental analysis ,ESI-MS and 1 H NMR spectra .Conclusion Treatment of purpurin-18 (2) with amines can produce target compounds 1a~1j .The starting raw material was inexpensive and readily available .The reaction conditions were mild and workup was convinient .