Pyrroloquinoline and pyridoacridine alkaloids from marine sources.
Marine organisms are a rich source for natural products. Pyrrolo[4,3, 2-de]quinolines and pyrido[4,3,2-mn]acridines are of major interest as metabolites in sponges and ascidians. Many of these compounds have generated interest both as challenging problems for structure elucidation and synthesis as well as for their cytotoxicities. The isolation, structure proof, biological activities, chemical properties and synthesis have attracted the attention of chemists, biologists and pharmacists. The principal structural feature of these alkaloids is the core of a planar iminoquinone moiety which can intercalate into DNA and cleave the DNA double helix or inhibit the action of topoisomerase II. Of the makaluvamines, makaluvamine F and A are the most cytotoxic to the HCT 116 cell line. The enhanced toxicity of the makaluvamines towards xrs-6 cells shows that all of the makaluvamines, except makaluvamine B, act like m-AMSA and etoposide in inhibiting topo iso merases via cleavable complex formation, or via the direct induction of DNA double-strand breaks. They are also amongst the most potent inhibitors of topoisomerase II. Both makaluvamine A and C can decrease tumor size in a solid human tumor model. Discorhabdin A and C in contrast are of high cytotoxicity, but they exhibit no inhibition of topoisomerase II. As representatives of the derivatives of pyrido[4,3,2-mn]acridine, cystodytins, kuanoniamines and diplamine are the most potent to inhibit HCT replication. Eilatin, as a 1,10-phenanthroline derivative, can form complexes with metal ions. It has been shown that these metal complexes can bind to DNA by intercalation. The new members of the pyrrolo[4,3,2-de]quinolines and pyrido[4,3, 2-mn]acridines, such as veiutamine, discorhabdin G, tsitsikammamines, epinartins, arnoamines as well as sagitol are reviewed. Some successful syntheses of pyrrolo[4,3,2-de]quinoline ring system and pyrido[4,3,2-mn]acridine ring system are also reviewed in this article.
Ding
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Department of Chemistry University of Alberta Edmonton, Alberta, T6G 2G2 Canada.
Chichak
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Lown
J W
JW
D000166:Acridines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D007364:Intercalating Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008386:Marine Biology; D011726:Pyridinium Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors
D000166:Acridines; D000470:Alkaloids; D007364:Intercalating Agents; D011726:Pyridinium Compounds; D011758:Pyrroles; D011804:Quinolines; D059005:Topoisomerase II Inhibitors