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1.
Bioorg Med Chem ; 22(5): 1608-19, 2014 Mar 01.
Article in English | MEDLINE | ID: mdl-24530030

ABSTRACT

1,2,3-Triazole-, arylamino- and thio-substituted naphthoquinones (24, 8, and 2 representatives, respectively) were synthesized in moderate yields and evaluated against several human cancer cell lines (blood, ovarian, breast, central nervous system, colon, and prostate cancers and melanoma), showing, for some of them, IC50 values below 2 µM. The cytotoxic potential of the tested naphthoquinones was also assayed on non-tumor cells such as human peripheral blood mononucluear cells (PBMC) and two murine fibroblast lines (L929 and V79 cells). α-Lapachone- and nor-α-lapachone-based 1,2,3-triazoles and arylamino-substituted naphthoquinones showed potent cytotoxicity against different cancer cell lines. The compounds may represent promising new lead derivatives for anticancer drug development. The electrochemical properties of selected compounds were evaluated in an attempt to correlate them with antitumor activity.


Subject(s)
Naphthoquinones/chemistry , Triazoles/chemistry , Cell Proliferation , Click Chemistry , Humans , Models, Molecular , Molecular Structure , Structure-Activity Relationship
2.
Bioorg Med Chem ; 21(21): 6337-48, 2013 Nov 01.
Article in English | MEDLINE | ID: mdl-24074878

ABSTRACT

In our continued search for novel trypanocidal compounds, twenty-six derivatives of para- and ortho-naphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Compounds 17-24, 28-30 and 36-38 are described herein for the first time. Three of these novel compounds (28-30) were found to be more potent than the standard drug benznidazole, with IC50/24h values between 6.8 and 80.8µM. Analysis of the toxicity to heart muscle cells led to LC50/24h of <125, 63.1 and 281.6µM for 28, 29 and 30, respectively. Displaying a selectivity index of 34.3, compound 30 will be further evaluated in vivo. The electrochemical properties of selected compounds were evaluated in an attempt to find correlations with trypanocidal activity, and it was observed that more electrophilic quinones were generally more potent.


Subject(s)
Naphthoquinones/chemistry , Triazoles/chemistry , Trypanocidal Agents/chemical synthesis , Animals , Cell Survival/drug effects , Cells, Cultured , Crystallography, X-Ray , Electrochemical Techniques , Electrodes , Mice , Molecular Conformation , Myocytes, Cardiac/cytology , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/toxicity , Trypanocidal Agents/chemistry , Trypanocidal Agents/toxicity , Trypanosoma cruzi/drug effects
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