Synthesis and antitumor evaluation of desmosdumotin C derivatives on B-ring / 中国药学杂志

OBJECTIVE: To synthesize desmosdumotin C derivatives on B-ring with antitumor activity. METHODS: The target compounds were synthesized from 2, 4, 6-trihydroxyacetophenone via methylation, O-methylation and aldol reaction. Their antiproliferative activities were tested against six human tumor cell lines. RESULTS: Fourteen target compounds were synthesized, nine of which were new compounds. All of them were characterized using 1H-NMR, 13C-NMR and MS. CONCLUSION: Preliminary pharmacological test showed that all the title compounds except 1i exhibited potent antitumor activities. 1h and 1n were better than desmosdumotin C in vitro. Introducing two fluoro atom on B-ring would benefit its activity against some tumor cells.

Synthesis and antitumor activity of fluoroquinolone C-3 heterocycles-oxadiazole derivatives (II) / 中国药学杂志

OBJECTIVE: To discover an efficient route for the conversion of an antibacterial fluoroquinolone to an antitumor one. METHODS: Cyclo-condensation of ofloxacin hydrazide 2 with aromatic carboxylic acids in POCl3 gave the corresponding oxadiazole derivatives 3a-3j, and their antitumor activity was evaluated by MTT assay. RESULTS: Ten title compunds were synthesized and showed potential antitumor activity. CONCLUSION: Heterocycles as isosteric replacement of carboxyl are warrant further development.

Synthesis of fluoroquinolone C-3 heterocycles, bis-oxadiazole methylsulfides and methiodides, and their antitumor activity / 中国药学杂志

OBJECTIVE: To explore an efficient structure modification route to transform antibacterial fluoroquinolones to antitumor ones. METHODS: Compound A[1,3,4] oxadiazol-5-thiol 3 derived from ofloxacin 1 was subjected to nucleophilic substitution with each of chloromethyl-1,3,4-oxadiazoles 4a-4g gave di-oxadiazolyl methylsulfides 5a-5g, followed by a quaternization to form the corresponding methiodides 6a-6g, respectively. The in vitro antitumor activity of the title compounds 5a-5g and 6a-6g against three cancer cell lines was evaluated by MTT method. RESULTS: Fourteen title compunds were synthesized and the structures were characterized by corresponding spectral data. The bioactive assay showed that compounds 5a-5g and 6a-6g exhibited a potential anticancer activity (IC50 < 25 μmol · L-1). The activity of the quaternary ammoniums 6a-6g was higher than that of the corresponding free bases 5a-5g. CONCLUSION: The design and synthesis of antitumor fluoroquinolone based on antibacterial fluoroquinolone C-3 heterocycle are worthy of further study.