ABSTRACT
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.
ABSTRACT
Cancer stem cells play a crucial role in tumors'invasion, metastasis, recurrence and drug resistance.Investigation on the chemicals with tumor stem cell growth inhibitory activity has been greatly highlighted in the field of anti-tumor drug discovery.This paper briefly reviews the recent progress of chemical investigations on substances with tumor stem cell growth inhibitory activity , aiming to give readers a reference on anti-tumor drug discovery.
ABSTRACT
Objective To develop an HPLC method for the simultaneous determination of 7-ethyl-10-hydroxycamptothecin-10-palmitic acid ester(SN38-PA)and its active metabolite 7-ethyl-10-hydroxycamptothecin(SN38)in rat plasma. Methods The inter standard was 10-hydroxycamptothecin. The protein in plasma was precipitated with methanol after acidification with formic acid. SN38-PA and SN38 were separated on Agilent C18 column(4.6 mm×250 mm,5μm) with gradient elution by using the mobile phase of methanol-0.2% formic acid solution. The flow rate was 1 ml/min. The detection wavelength was set at 372 nm. The column temperature was maintained at 30℃. Results The linear ranges for SN38-PA and SN38 were 0.25-62.5(r=0.9998) and 0.05-12.5 μg/ml (r=0.9997) respectively. The limits of quantification were 0.18 and 0.04 μg/ml, respectively. The average relative recovery of SN38-PA and SN38 were 95.89% and 97.03%. The average absolutely recovery of SN38-PA and SN38 were 99.54% and 99.84%. The RSD for intra-day and inter-day were both less than 3%. Conclusion The method is fast, convenient, accurate and sensitive, so it can be used for determination of SN38-PA and SN38 in vivo.