Synthesis and cytotoxic activity of conjugates of muramyl and normuramyl dipeptides with batracylin derivatives.
The synthesis of MDP (muramyl dipeptide) or nor-MDP (normuramyl dipeptide) conjugates modified at the peptide part with batracylin (BAT) or batracylin derivatives is described. Batracylin was synthesized by our modified method (Scheme 3). The synthesis of BAT via this modified route now appears to be feasible on a multigram scale. Preliminary screening data obtained at the National Cancer Institute (NCI, Bethesda, MD) have revealed that the conjugates did not expose any cytotoxic activity even at 10(-4)-10(-8) M or microg/mL. During tests performed at Medical University of Gdansk, Poland, two analogues 11c and 11e reduced the proliferation of Ab melanoma cells in vitro compared with batracylin alone (Table 2, Figure 1).
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
Trzonkowski
Piotr
P
Sewerynek
Przemysław
P
Myśliwski
Andrzej
A
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006224:Cricetinae; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004151:Dipeptides; C472798:N-(1-O-benzyl-N-acetylmuramuyl-valyl-gamma-isoglutaminyl)batracylin; C472797:N-(1-O-benzyl-N-acetylnormuramyl-alanyl-gamma-isoglutaminyl)batracylin; D011799:Quinazolines; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C057924:batracylin