Add time:09/08/2019         Source:sciencedirect.com

The amino acid-conjugates (1a–k) with eleven amino acids attached to primary amine of (S)-1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-one (DW2282, 1) were prepared and studied for their prodrug characteristics and anti-cancer activity against SW620 cell line. All the amino acid derivatives showed not only improved water solubility but also displayed potent anti-cancer activity in vitro. Among these amino acid-conjugates the compounds, DW2282-l-Ala (1b), DW2282-l-Phe (1e), DW2282-l-Leu (1g) and DW2282-l-Met (1h) showed good reconversion within 8 h (104.76%, 84.03%, 95.02% and 78.34%, respectively) to the parent drug in human plasma. In addition, the compounds 1e, 1g and 1j also showed good bioavailability profile along with potent in vivo anticancer activity.

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