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

Xanthones and Cancer: from Natural Sources to Mechanisms of Action

“…Most of these compounds had moderate cytotoxicity against tumor cells. On the other hand, benzoxanthone derivatives showed potent topoisomerase I inhibitory effect, indicating the potential for these compounds for development as non‐camptothecin topoisomerase I inhibitors …”

“…a) Br 2 (2 equiv. ), AcOH, r.t.; b) benzyl bromide, K 2 CO 3 , acetone and c) 3‐methoxybenzoyl chloride, Et 3 N, acetone, r.t., then 3‐bromobenzoyl chloride, NaH, THF (dry), r.t …”

“…On the other hand, benzoxanthone derivatives showed potent topoiso-merase I inhibitory effect, indicating the potential for these compounds for development as non-camptothecin topoisomerase I inhibitors. [150] Prenylated xanthones belong to a class of secondary metabolites that are particularly common in plants. Interest in these compounds has increased because they demonstrate important biological potential in which the prenyl moieties can lead to increased binding affinity to proteins and higher membrane Scheme 4.…”

“…a) Br 2 (2 equiv. ), AcOH, r.t.; b) benzyl bromide, K 2 CO 3 , acetone and c) 3-methoxybenzoyl chloride, Et 3 N, acetone, r.t., then 3-bromobenzoyl chloride, NaH, THF (dry), r.t. [150] permeability by their lipophilic nature. To create a structureÀ activity relationship (SAR) involving the presence of prenyl groups, some prenylated xanthones have been synthesized.…”

Topoisomerase as target for antibacterial and anticancer drug discovery

“…Ongoing phase I 65 studies suggest that this drug has higher therapeutic index with prolonged administration. CPT-11 64 , Figure 5 (14), also known as irinotecan used for the treatment of lung, cervical and ovarian cancer. CPT-11 was recently approved in the USA for the treatment of colorectal cancer 45,66 .…”