First syntheses of melophlins P, Q, and R, and effects of melophlins on the growth of microorganisms and tumor cells.
The marine tetramic acid (=1,5-dihydro-4-hydroxy-2H-pyrrol-2-ones) derivatives melophlin P, Q, and R (1p-1r, resp.) were synthesized for the first time in only four steps. Together with the congenerous melophlins A-C and G, they were also tested for antimicrobial and cytotoxic effects. Melophlins B, C, P, Q, and R, which share a 5-Me residue, showed some antibacterial activity, mainly in Gram-positive bacteria. Melophlins B, C, and R, which have Me-branched 3-acyl side chains in common, inhibited the growth of cells of human KB-3-1 cervix carcinoma, A-498 kidney carcinoma, and U-937 leukemia with IC(50) values <10 muM. They were similar in activity to cisplatin. Melophlin Q, also Me-branched, was astoundingly specific in inhibiting A-498 kidney cancer cells, while melophlin P inhibited U-937 leukemia cells particularly well. The position of the Me branch is decisive for the magnitude of the antiproliferative effect of the melophlin couples B/C and R/Q.
Biersack
Bernhard
B
Organisch-chemisches Laboratorium der Universität Bayreuth, Universitätsstrasse 30, NW 1, D-95447 Bayreuth.
Diestel
Randi
R
Jagusch
Carsten
C
Rapp
Georg
G
Sasse
Florenz
F
Schobert
Rainer
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D011760:Pyrrolidinones