Park, Seojeong; Hong, Eunji; Kwak, Soo Yeon; Jun, Kyu-Yeon; Lee, Eung-Seok; Kwon, Youngjoo; Na, Younghwa published the artcile< Synthesis and biological evaluation of C1-O-substituted-3-(3-butylamino-2-hydroxy-propoxy)-xanthen-9-one as topoisomerase IIα catalytic inhibitors>, COA of Formula: C8H8BrCl, the main research area is xanthone preparation topoisomerase IIa catalytic inhibitory anticancer activity; Anticancer agents; C1-alkyl and arylalkyl substituted xanthones; Topoisomerase IIα catalytic inhibitor.
Topoisomerase II poison blocks the transitorily generated DNA double-strand breaks (DSBs) from religation, thereby causes severe DNA damage and gene toxicity. While topoisomerase II catalytic inhibitor does not form cleavable DNA-enzyme complex because its function attributes to inhibition of the catalytic steps of the enzyme such as before generating DNA DSBs or in the last step of the catalytic cycle after religation. It has been reported that the stabilizing effect of etoposide on transient cleavable DNA-topoisomerase IIβ complex attributes to its secondary malignancy. Therefore, topoisomerase IIα has been considered as more attractive target than topoisomerase IIβ for the development of chemotherapeutic agents. In the previous work, we reported compounds as novel topoisomerase IIα catalytic inhibitors targeting for ATP binding site of human topoisomerase IIα ATP-binding domain. As a continuous work, we have designed and synthesized 43 compounds of C1-O-alkyl and arylalkyl substituted compounds with or without methoxy group on ring A. In the topoisomerase IIα inhibitory test, among the tested C1-O-4-chlorophenethyl substituted compounds I (R1 = H, OMe) were more active than others, and compound I (R1 = H) showed strongest topoisomerase IIα inhibitory activity with 94.4% and 23.0% inhibition, resp., at 100 and 20 μM. Compounds I (R1 = H, OMe) have also showed much enhanced cytotoxic activity against T47D cells; IC50 (μM): 0.63 ± 0.01 and 0.19 ± 0.02, resp., which are stronger than reference drugs. Band depletion assay and cleavage complex assay results showed compounds I (R1 = H, OMe) were potential topoisomerase IIα catalytic inhibitor with low DNA damage.
European Journal of Medicinal Chemistry published new progress about Antitumor agents. 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, COA of Formula: C8H8BrCl.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics