title: Combination of amino acid/dipeptide with nitric oxide donating oleanolic acid derivatives as PepT1 targeting antitumor prodrugs.
abstract: By taking advantage of the cytotoxic effect of nitric oxide (NO) and PepT1 for molecule-targeted drug delivery, a series of amino acid/dipeptide diester prodrugs of NO-donating oleanolic acid derivatives were designed and synthesized. Two prodrugs 6a and 8a showed potent cytotoxcity, which is probably due to their high PepT1 affinity and NO-releasing ability. Furthermore, the aqueous solubility of the prodrugs was also significantly enhanced because of the hydrophilic amino acid/dipeptide promoiety.
authors.affiliation: Pharmaceutical Research Center and Jiangsu Province Hi-Tech Key Laboratory for Bio-Medical Research, School of Chemistry and Chemical Engineering, Southeast University , Nanjing 211189, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gou
authors.forename: Xuying
authors.initials: X
authors.lastname: Liu
authors.forename: Huan
authors.initials: H
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
mesh_terms: D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004151:Dipeptides / Q000737:chemistry* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004952:Esters; D007583:Jejunum / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000737:chemistry* / Q000494:pharmacology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D000074011:Peptide Transporter 1; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship; D027981:Symporters / Q000378:metabolism*; D014867:Water
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D004151:Dipeptides; D004952:Esters; D020030:Nitric Oxide Donors; D000074011:Peptide Transporter 1; D011355:Prodrugs; D027981:Symporters; D014867:Water; C004194:glycylsarcosine; D009828:Oleanolic Acid