Marine pyridoacridine alkaloids: structure, synthesis, and biological chemistry

The Total Synthesis of Neoamphimedine

“…The solid was recrystallized with CHCl 3 and hexanes to give yellow crystals (2.4 mg, 30% yield). The original publication of the structure of neoamphimedine NMR data was reported in trifluoroacedic acid (TFA), It is important to note that neoamphimedine is unstable in the presence of TFA: TLC (CHCl 3 …”

“…These include generating reactive oxygen species (ROS), binding to transition metals, and inhibiting topoisomerases. [2][3][4] Topoisomerase II (top2) is an important molecular target for chemotherapeutic drug discovery. [4][5][6][7] Besides the ability to relax supercoiled DNA top2 also catalyzes the decatenation and catenation of DNA.…”

“…2,7 Pyridoacridine derivatives have been shown to target topoisomerase function, while a few can stabilize the top2 cleavable complex, most inhibit top2 catalytic function. [2][3][4] Recently we reported the antineoplastic and novel top2 mediated cytotoxicity of neoamphimedine (2) (Chart 1). 8,9 In vitro, 2 has top2 dependent cytotoxicity in JN394T2 yeast cells as well as potent cytotoxicity in mammalian tumor cells, particularly the HCT116 cell line and the MDR1 expressing A2780AD cell line.…”

Alkaloids from Marine Invertebrates as Important Leads for Anticancer Drugs Discovery and Development

“…[102]. Since then, more than 80 pyridoacridines have been found in many marine organisms such as sponges, tunicates, anemones, and mollusks [100,103,104]. Most pyridoacridines have been reported to have significant cytotoxicity due to a highly planar electron-deficient aromatic ring system that can intercalate DNA, resulting in the inhibition of cell growth [105].…”

Interaction of quinone diimides of the 10H-9-thia-10-aza-phenanthrene 9,9-dioxide series with sodium p-toluenesulfinate and hydrogen chloride

“…6 Interest in these compounds has increased during the last 25 years due to the significant biological properties of many naturally occurring heterocyclic quinone imides isolated from marine sponges, tunicates, and mollusks. [7][8][9] The regioselective addition of HCl to unsubstituted unsymmetrical benzoquinone diimines was first reported by Adams, who observed that 1,4-addition of chloride anion occurs at the ring position meta to the most basic nitrogen. 10 Later this rule for the orientation of the chloride anion was revised to take account of the comparative stability of the isomeric quinonoid intermediates based on the oxidation-reduction potentials of p-benzoquinone monoimides with analogous substituents at nitrogen.…”