Inhibition of ABCG2-mediated drug efflux by naphthopyrones from marine crinoids

Five new napthopyrones were isolated from marine crinoids as part of a screen looking for inhibitors of ABCG2-mediated efflux. Six known metabolites were isolated with the new compounds. Only the angular napthopyrones were active against ABCG2-mediated efflux. Five new naphthopyrones ( 1– 5) along with the known compounds TMC-256A1, 5,8-dihydroxy-6-methoxy-2-propyl-4 H-naphtho[2,3- b]pyran-4-one, TMC-256C1, comaparvin, 6-methoxycomaparvin, and 6-methoxycomaparvin 5-methyl ether ( 6– 11) were isolated from crinoids of the family Comasteridae. All compounds were tested for their ability to inhibit the multidrug transporter ABCG2, which plays a role in drug resistance. Six of the seven angular naphthopyrones showed moderate activity with