Synthesis and antitumor activity of conjugates of muramyldipeptide or normuramyldipeptide with hydroxyacridine/acridone derivatives.
A series of MDP (muramyldipeptide) or nor-MDP (normuramyldipeptide) analogues modified at the C-terminus post of the molecule by a formation of an ester bond between the carboxylic group of isoglutamine and the hydroxyl function of the respective derivatives of 4-carboxamide-acridine/9-acridone or 1-nitro-9-hydroxyalkylaminoacridines were synthesized as potential anticancer agents. The compounds O-(1-O-benzyl-N-acetyl-muramyl-l-alanyl-d-gamma-isoglutaminyl)-9-(ethylamino)-1-nitroacridine ester 3j and O-(1-O-benzyl-N-acetyl-muramyl-l-alanyl-d-gamma-isoglutaminyl)-9-propylamino-1-nitroacridine ester 3k exhibited high in vitro cytotoxic activity against a panel of human cell lines, prostate cancer and AIDS-related lymphoma (ARL). Analogue 3j was also active in vivo in the hollow fiber assay. Antitumor activity of both compounds were tested in vivo against difference human tumor xenograft, but only analogue 3k showed in vivo activity against sc UACC-62 melanoma in mice.
Dzierzbicka
Krystyna
K
Department of Organic Chemistry, Gdansk University of Technology, 11/12 G. Narutowicza Street, 80-952 Gdansk, Poland. kd@chem.pg.gda.pl
Kołodziejczyk
Aleksander M
AM
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000166:Acridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054831:Acridones; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000166:Acridines; D054831:Acridones; D000970:Antineoplastic Agents; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C041300:acridone