title: Investigation of amino acid conjugates of (S)-1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-one (DW2282) as water soluble anticancer prodrugs.
abstract: 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.
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Ki-Cheul
authors.initials: KC
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Eeda
authors.initials: E
authors.lastname: Venkateswararao
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Vinay Kumar
authors.initials: VK
authors.lastname: Sharma
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: jungshh@cnu.ac.kr.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Jung
mesh_terms: D000588:Amines / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D004355:Drug Stability; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D012995:Solubility; D013450:Sulfones / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D014867:Water / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000588:Amines; D000596:Amino Acids; D000970:Antineoplastic Agents; D007093:Imidazoles; D011355:Prodrugs; D013450:Sulfones; D014867:Water; C404303:DW 2282
keywords: Amino acid conjugates; Anti-cancer; Imidazolidinone; Prodrug