Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Database
Language
Publication year range
1.
Yao Xue Xue Bao ; 50(8): 1008-12, 2015 Aug.
Article in Chinese | MEDLINE | ID: mdl-26669001

ABSTRACT

To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, ß-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, ß-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Fluoroquinolones/chemical synthesis , Fluoroquinolones/pharmacology , Amides/chemical synthesis , Amides/pharmacology , Cell Line, Tumor , HL-60 Cells , Humans , Ketones/chemical synthesis , Ketones/pharmacology , Rhodanine/chemical synthesis , Rhodanine/pharmacology
2.
Yao Xue Xue Bao ; 50(5): 569-73, 2015 May.
Article in Chinese | MEDLINE | ID: mdl-26234138

ABSTRACT

To discover novel antitumor fluoroquinolone lead compounds from a rational modification for antibacterial fluoroquinolones, a fused heterocyclic ketone corresponding to thiazolo[2,3- b][1,2,4]triazolone used as a bioisosteric replacement of the C-3 carboxylic acid group of ciprofloxacin 1, and further modification by a Claisen condensation reaction with substituted benzaldehydes formed novel fluoroquinolone C-3 fuse heterocyclic α, ß-unsaturated ketones as the title compounds (6a-6r), separately. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS, and the in vitro anti-proliferative activity against human hepatoma Hep-3B cells, pancreatic Capan-1 cells and leukemia HL60 cells was evaluated by a MTT assay. The preliminary results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. In particular, compounds carrying an electron-withdrawing carboxyl (6k, 6m) or sulfonamide substituent (6q, 6r) attached to benzene ring were comparable to or better than constractive drug doxorubicin against Capan-1 cells. As such, it suggests that it is favorable for a fused heterocyclic α, ß-unsaturated ketone scaffold instead of the C-3 carboxylic acid group to improve the antitumor activity of fluoroquinolones.


Subject(s)
Antineoplastic Agents/pharmacology , Ciprofloxacin/analogs & derivatives , Fluoroquinolones/pharmacology , Ketones/pharmacology , Anti-Bacterial Agents , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Fluoroquinolones/chemical synthesis , HL-60 Cells , Humans , Structure-Activity Relationship
3.
Yao Xue Xue Bao ; 50(3): 332-6, 2015 Mar.
Article in Chinese | MEDLINE | ID: mdl-26118113

ABSTRACT

To discover novel fluoroquinolone lead compounds as possible anti-infective or/and antitumor chemotherapies, combination principle of pharmacophore-based drug design, a series of novel tricyclic fluoroquinolone title compounds, [1,2,4]triazino[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives ( 5a-5p), were designed and synthesized with a fused [1,2,4]-triazine ring unit. Their structures were characterized by spectral data and elemental analysis and the in vitro antibacterial and anti-cell proliferation activities were also evaluated. The results showed that the titled compounds exhibited more significant inhibitory activities against drug-resistant bacteria (Methicillin-resistant Staphylococcus aureus and multi drug-resistant Escherichia coli strains) and three tested cancer cell lines (human hepatoma SMMC-7721, murine leukemia L1210 and human murine leukemia HL60 cells). Interestingly, SAR showed that compounds with electron-donating groups attached to benzene ring had stronger antibacterial activity than antitumor activity, but electron-withdrawing compounds displayed more potential antitumor activity than antibacterial activity, especially antitumor activity of nitro compounds was comparable to comparison doxorubicin. Thus, novel triazine-fused tricyclic fluoroquinolones as potent anti-infective or/and antitumor lead compounds are valuable to pay attention and for further development.


Subject(s)
Anti-Bacterial Agents/chemistry , Antineoplastic Agents/chemistry , Drug Design , Fluoroquinolones/chemistry , Animals , Anti-Bacterial Agents/chemical synthesis , Antineoplastic Agents/chemical synthesis , Carboxylic Acids , Carcinoma, Hepatocellular , Cell Line , Cell Proliferation , Escherichia coli/drug effects , Fluoroquinolones/chemical synthesis , HL-60 Cells , Humans , Leukemia L1210 , Liver Neoplasms , Methicillin-Resistant Staphylococcus aureus/drug effects , Mice , Naphthyridines , Triazines
4.
Yao Xue Xue Bao ; 50(10): 1258-62, 2015 Oct.
Article in Chinese | MEDLINE | ID: mdl-26837171

ABSTRACT

To discover an efficient strategy for the conversion of the antibacterial activity of fluoroquinolones into the antitumor activity, the three series of C-3 s-triazole-based derivatives including sulfide ketones (6a-6g), thiosemicarbazones (7a-7g) and fused heterocyclic thiazolotriazoles (8a-8g) were synthesized from ciprofloxacin (1), respectively. The structures were characterized by elemental analysis and spectral data. The antitumor activity was tested against three tumor cell lines (Hep-3B, Capan-1 and HL60) using the MTT assay. The three types of compounds all exhibited stronger anti-proliferative activities than ciprofloxacin in the test. The order of their activities was in compounds 7>8>6, and the order of selectivity against cancer cell lines was Capan-1, Hep-3B and HL60. Meanwhile, the SAR revealed that some compounds with electron-drawing group substituted such as fluoro- and nitro-phenyl compounds (6f, 7f, 8f) and (6g, 7g, 8g) displayed more significant activity than the control compounds, especially the IC50 values of thiosemicarbazone compounds 7f and 7g against Capan-1 was comparable to doxorubicin. Thus, a five-membered triazole as the C-3 bioisostere modified with the functionalized side-chain of sulfide-ketone thiosemicarbazone warrants special attention and further investigation.


Subject(s)
Antineoplastic Agents/pharmacology , Ciprofloxacin/chemistry , Ketones/pharmacology , Triazoles/pharmacology , Anti-Bacterial Agents/chemistry , Cell Line, Tumor , Doxorubicin/pharmacology , HL-60 Cells , Humans , Sulfides/pharmacology
5.
Yao Xue Xue Bao ; 49(12): 1694-8, 2014 Dec.
Article in Chinese | MEDLINE | ID: mdl-25920199

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.


Subject(s)
Antineoplastic Agents/chemistry , Fluoroquinolones/chemistry , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Humans , Oxadiazoles/chemistry , Structure-Activity Relationship
SELECTION OF CITATIONS
SEARCH DETAIL
...