To contribute to the development of an efficient method for the conversion of antibacterial fluoroquinolones to antitumor fluoroquinolones,a series of C3/C3 bis-fluoroquinolone fused heterocycles cross-linked with a[1,2,4]-triazolo[3,4-b][1,3,4]-thiadiazole core as a common bioisostere of two carboxylic acid groups was designed and synthesized as their hydrochloride salts.Structures were characterized by elemental analysis and spectral data and their in vitro antitumor activity against L1210,CHO and HL60 cell lines was screened by determination of their IC50 values in the methylthiazole trazolium(MTT)assay.Two compounds were highly potent against the HL60 cell line and represent promising lead compounds for future development.
The aim of this research was to produce novel antitumor fluoroquinolones from antibacterial analogs by introduction of a heterocyclic ring as a bioisostere of the C-3 carboxylic acid group.To this end,two series of eleven s-triazole derivatives bearing functionalized side chains of Schiff bases and Schiff Mannich bases were designed and synthesized.Structures were characterized by elemental analysis and spectral data after which in vitro antitumor activity against L1210,CHO and HL60 cell lines was evaluated in the MTT assay.Compounds posssing a free phenol group were particularly active and warrant further development.
Novel tricyclic fluoroquinolones,[1,2,4]triazolo[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives 4a-4h bearing carrying a functional Mannich-base moiety at the C-8 position,were synthesized and evaluated for their antimicrobial activity.The results showed that some compounds with a piperazine side chain exhibited comparable or better antibacterial activity than comparator cirprofloxacin.Furthermore,the targeted compounds also displayed a broad spectrum of activity against resistant strains including both Gram-negative and Gram-positive bacteria.In particular,compound 4h showed an MIC of 0.25 μg/mL in antibacterial assay against multiple drug-resistant Escherichia coli,which represents an about 30-fold increase of potency compared to ciprofloxacin.Thus,their excellent antibacterial activity against resistant strains suggests that triazole-fused fluoroquinolones warrant further optimization as novel anti-infective chemotherapies.
Liu-Zhou GaoYu-Suo XieTao LiWen-Long HuangGuo-Qiang Hu
To discover an efficient route for the shift from an antibacterial fluoroquinolone to an antitumor one based on the mechanistic similarities between targeting topoisomerases and the eukaryotic ones,two series of the title compounds,C3 bis-oxadiazole methylsulfides 6a―6h and corresponding dimethylpiperazinium iodides 7a―7h derived from levofloxacin 1 were designed and synthesized.Their in vitro antiproliferative activities against Chinese hamster ovary cell line（CHO）,murine leukemia cell line（L1210） and human leukocytoma cell line（HL60） were evaluated by MTT assay,and inhibitory effect on DNA topoisomerase IIα was also measured by means of densitometric assay.
HU Guo-qlangWANG Guo-qiangDUAN Nan-nanWEN Xiao-yiCAO Tie-yaoXIE Song-qiangHUANG Wen-long
