Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Molecules ; 20(6): 10689-704, 2015 Jun 10.
Article in English | MEDLINE | ID: mdl-26065834

ABSTRACT

Herpes simplex virus infections have been described in the medical literature for centuries, yet the the drugs available nowadays for therapy are largely ineffective and low oral bioavailability plays an important role on the inefficacy of the treatments. Additionally, the details of the inhibition of Herpes Virus type 1 are still not fully understood. Studies have shown that several viruses encode one or more proteases required for the production new infectious virions. This study presents an analysis of the interactions between HSV-1 protease and benzoxazinone derivatives through a combination of structure-activity relationships, comparative modeling and molecular docking studies. The structure activity relationship results showed an important contribution of hydrophobic and polarizable groups and limitations for bulky groups in specific positions. Two Herpes Virus type 1 protease models were constructed and compared to achieve the best model which was obtained by MODELLER. Molecular docking results pointed to an important interaction between the most potent benzoxazinone derivative and Ser129, consistent with previous mechanistic data. Moreover, we also observed hydrophobic interactions that may play an important role in the stabilization of inhibitors in the active site. Finally, we performed druglikeness and drugscore studies of the most potent derivatives and the drugs currently used against Herpes virus.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Benzoxazines/chemistry , Benzoxazines/pharmacology , Herpesvirus 1, Human/drug effects , Herpesvirus 1, Human/enzymology , Models, Molecular , Peptide Hydrolases/chemistry , Binding Sites , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Molecular Conformation , Molecular Docking Simulation , Molecular Weight , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Protein Binding , Structure-Activity Relationship
2.
Molecules ; 19(5): 6651-70, 2014 May 22.
Article in English | MEDLINE | ID: mdl-24858098

ABSTRACT

As part of a continuing search for new potential anticancer candidates, we describe the synthesis, cytotoxicity and mechanistic evaluation of a series of 4-oxoquinoline-3-carboxamide derivatives as novel anticancer agents. The inhibitory activity of compounds 10-18 was determined against three cancer cell lines using the MTT colorimetric assay. The screening revealed that derivatives 16b and 17b exhibited significant cytotoxic activity against the gastric cancer cell line but was not active against a normal cell line, in contrast to doxorubicin, a standard chemotherapeutic drug in clinical use. Interestingly, no hemolytical activity was observed when the toxicity of 16b and 17b was tested against blood cells. The in silico and in vitro mechanistic evaluation indicated the potential of 16b as a lead for the development of novel anticancer agents against gastric cancer cells.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor/drug effects , Cell Membrane/drug effects , Chemistry Techniques, Synthetic , Computer Simulation , Doxorubicin/pharmacology , Drug Screening Assays, Antitumor , Erythrocytes/drug effects , Hemolytic Agents/pharmacology , Humans , Inhibitory Concentration 50 , Mice , Molecular Docking Simulation , Molecular Structure , Quinolones/chemistry , Stomach Neoplasms/drug therapy
SELECTION OF CITATIONS
SEARCH DETAIL
...