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Synthesis and Biological Evaluation of Novel Water-Soluble Poly-(ethylene glycol)-10-hydroxycamptothecin Conjugates.

ABSTRACT: In order to improve the antitumor activity and water solubility of 10-hydroxycamptothecin (HCPT), a series of novel HCPT conjugates were designed and synthesized by conjugating polyethylene glycol (PEG) to the 10-hydroxyl group of HCPT via a valine spacer. The in vitro stability of these synthesized compounds was determined in pH 7.4 buffer at 37 °C, and the results showed that they released HCPT at different rates. All the compounds demonstrated significant antitumor activity in vitro against K562, HepG2 and HT-29 cells. Among them, compounds, 4a, 4d, 4e and 4f, exhibited 2-5 times higher potency than HCPT. The stability and antitumor activity of these conjugates were found to be closely related to the length of PEG and the linker type, conjugates with a relatively short PEG chain and carbamate linkages (compounds 4a and 4f) exhibited controlled release of HCPT and excellent antitumor in vitro activity.

SUBMITTER: Guo N

PROVIDER: S-EPMC6272474 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Synthesis and Biological Evaluation of Novel Water-Soluble Poly-(ethylene glycol)-10-hydroxycamptothecin Conjugates.

Guo Na N Jiang Du D Wang Luyao L You Xing X Teng Yu-Ou YO Yu Peng P

Molecules (Basel, Switzerland) 20150521 5

In order to improve the antitumor activity and water solubility of 10-hydroxycamptothecin (HCPT), a series of novel HCPT conjugates were designed and synthesized by conjugating polyethylene glycol (PEG) to the 10-hydroxyl group of HCPT via a valine spacer. The in vitro stability of these synthesized compounds was determined in pH 7.4 buffer at 37 °C, and the results showed that they released HCPT at different rates. All the compounds demonstrated significant antitumor activity in vitro against K ...[more]

PMID: 26007190

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