New benzoxanthone derivatives as topoisomerase inhibitors and DNA cross-linkers

Intestinal P-glycoprotein inhibitors, benzoxanthone analogues

“…Eight benzoxanthone compounds were synthesized . Cell culture and molecular biology grade reagents, and HPLC analysis grade solvents were commercially provided as followed: Antibiotic–antimycotic agent and RPMI 1640 medium from Invitrogen (Carlsbad, CA, USA), foetal bovine serum from Wisent Inc (Québe, QC, Canada), DNM and acetonitrile from Merck (Darmstadt, Germany), PTX from Samyang Genex (Daejeon, Korea), [ 3 H]‐DNM (16 Ci/mmol) from PerkinElmer Life and Analytical Sciences (Boston, MA, USA), Human P‐gp membranes, BD Gentest™ ATPase assay kit from BD bioscience (Woburn, MA, USA), the internal standard 4‐hydroxybenzoic acid n ‐hexyl ester from Tokyo Kasei Kogyo (Tokyo, Japan) and other chemicals and reagents from Sigma‐Aldrich (St. Louis, MO, USA).…”

“…Benzoxanthone analogues, tetracyclic ring molecules derived from the tricyclic ring molecule xanthone, have been synthesized . Xanthones extracted from mangosteens ( Garcinia mangostana ) have been applied as traditional medicines because of their activity against oxidation, tumour, inflammation, bacteria, fungi, virus, etc .…”

“…Among the analogues, 1,3‐bis(oxiran‐2‐ylmethoxy)‐12 H ‐benzo[ b ]xanthen‐12‐one was the most effective inhibitor to target DNA‐topoisomerase II complex and DNA duplex. Another analogue, 8,10‐bis(thiiran‐2‐ylmethoxy)‐7 H ‐benzo[ c ]xanthen‐7‐one showed dual activity in DNA relaxation through effects on topoisomerases I and II . However, the P‐gp modulating effect of the benzoxanthone analogues has not been examined in vitro and in vivo yet.…”

Synthesis of novel benzoxanthone analogues as non-Camptothecin topoisomerase I inhibitors

“…In the 1 H NMR spectra, all non-substituted or monosubstituted on hydroxy benzoxanthones (1-6c) showed single peaks at δ 13.00 corresponding to the hydroxyl hydrogen adjacent to the carbonyl group in the benzoxanthone ring 7 . These single peaks disappeared in the 1 H NMR spectra of di-substituted derivatives (7a-e), which indicates the introduction of two substituted groups on two hydroxyl groups.…”

“…Based on our knowledge about topoisomerase I inhibitor, we designed 9,11-substituted benzoxanthones for improving their anti-cancer activities. However, Cho and co-workers 7 had designed a series of new benzoxanthone analogues possessing epoxy or thioepoxy groups during our study about benzoxanthone. They have synthesized 12 oxiranylmethoxy-or thiiranylmethoxysubstituted benzoxanthone analogues and compound 1,3-bis(oxiran-2-ylmethoxy)-12H-benzo[b]-xanthen-12-one as potent topoisomerase I and II inhibitor was the most efficient among these compounds.…”