Synthesis, antitumor activity and SAR of C-3 oxadiazole sulfanylacetylhydrazone-substituted fluoroquinolone analogues / 药学学报
Acta Pharmaceutica Sinica
; (12): 1694-8, 2014.
Article
in Zh
| WPRIM
| ID: wpr-457271
Responsible library:
WPRO
ABSTRACT
To explore an efficient strategy for the conversion of antibacterial fluoroquinolones into antitumor fluoroquinolones, an azole heterocyclic ring of oxadiazole instead of the C-3 carboxylic acid group with a functionalized hydrazone group as a modified side-chain, fifteen novel 2-(fluoroquinolon-3-yl)-oxadiazole-5- sulfanylacetylhydrazone derivatives 7a-7o were designed and synthesized on the basis of the pharmacophore hybridization principle from pefloxacin, separately. The structures for fifteen title compounds were characterized by elemental analysis, 1H NMR and MS, and their in vitro antitumor activity against Hep-3B cell line was evaluated by a MTT assay. The results showed that the title compounds exhibited more significantly inhibitory activity than that of the parent pefloxacin, in which compounds with electron-withdrawing group attached on aryl ring had more potency than that of compounds with electron donating group, especially compounds with a carboxylic substituent were comparable to comparison doxorubicin. It suggests that it is favorable for an improvement of antitumor activity to remain a carboxylic acid unit at the aromatic ring.
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WPRIM
Language:
Zh
Journal:
Acta Pharmaceutica Sinica
Year:
2014
Type:
Article