Antileishmanial activity of quinazoline derivatives: Synthesis, docking screens, molecular dynamic simulations and electrochemical studies

A series of quinazoline-2,4,6-triamine were synthesized and evaluated in vitro against Leishmania mexicana. Among them, N6-(ferrocenmethyl)quinazolin-2,4,6-triamine (H2) showed activity on promastigotes and intracellular amastigotes, as well as low cytotoxicity in mammalian cells. Docking and electr...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2015-03, Vol.92, p.314-331
Main Authors: Mendoza-Martínez, Cesar, Galindo-Sevilla, Norma, Correa-Basurto, José, Ugalde-Saldivar, Victor Manuel, Rodríguez-Delgado, Rosa Georgina, Hernández-Pineda, Jessica, Padierna-Mota, Cecilia, Flores-Alamo, Marcos, Hernández-Luis, Francisco
Format: Article
Language:English
Subjects:
Animals
Antiprotozoal Agents - chemical synthesis
Antiprotozoal Agents - chemistry
Antiprotozoal Agents - pharmacology
Antiprotozoan activity
Dose-Response Relationship, Drug
Electrochemical Techniques
Leishmania mexicana
Leishmania mexicana - cytology
Leishmania mexicana - drug effects
Macrophages - drug effects
Mice
Mice, Inbred BALB C
Molecular Docking Simulation
Molecular Dynamics Simulation
Molecular Structure
Parasitic Sensitivity Tests
Quinazoline
Solubility
Structure-Activity Relationship
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Summary:A series of quinazoline-2,4,6-triamine were synthesized and evaluated in vitro against Leishmania mexicana. Among them, N6-(ferrocenmethyl)quinazolin-2,4,6-triamine (H2) showed activity on promastigotes and intracellular amastigotes, as well as low cytotoxicity in mammalian cells. Docking and electrochemical studies showed the importance of both the ferrocene and the heterocyclic nucleus to the observed activity. H2 is readily oxidized electrochemically, indicating that the mechanism of action probably involves redox reactions. [Display omitted] •A quinazoline derivative (H2) as antileishmanial agent with low cytotoxicity was found.•H2 is active against promastigote and amastigote form of Leishmania mexicana.•H2 begins its antiparasitic action in less than 1 h, probably by oxidative mechanism.•H2 probably has a dual mechanism: oxidative stress inductor and DHFR inhibitors.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2014.12.051