One-pot microwave assisted synthesis of new 2-alkoxycarbonylmethylene-4-oxo-1,5-benzo-, naphtho-, and pyridodiazepines and assessment of their cytogenetic activity

1,5-Benzo-, naphtho-, and pyridodiazepines 3 have been synthesized in excellent yields in one-step from the reaction of o-phenylenediamines with acetonedicarboxylates through microwave assisted acid catalysis. In order to ascertain their cytogenetic activity in vitro at doses equivalent to the per o...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2013-09, Vol.67, p.302-309
Main Authors: Eleftheriadis, Nicolaos, Neochoritis, Constantinos G., Tsoleridis, Constantinos A., Stephanidou-Stephanatou, Julia, Iakovidou-Kritsi, Zafiroula
Format: Article
Language:English
Subjects:
1,5-Benzodiazepines
Azepines - chemical synthesis
Azepines - chemistry
Azepines - pharmacology
Cells, Cultured
Cytogenetic activity
Dose-Response Relationship, Drug
Humans
Lymphocytes - cytology
Lymphocytes - drug effects
Microwave irradiation
Microwaves
Molecular Structure
Proliferation Rate Index
Pyridines - chemical synthesis
Pyridines - chemistry
Pyridines - pharmacology
Sister Chromatid Exchange - drug effects
Sister Chromatid Exchange - genetics
Sister Chromatid Exchanges
Structure-Activity Relationship
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Summary:1,5-Benzo-, naphtho-, and pyridodiazepines 3 have been synthesized in excellent yields in one-step from the reaction of o-phenylenediamines with acetonedicarboxylates through microwave assisted acid catalysis. In order to ascertain their cytogenetic activity in vitro at doses equivalent to the per os doses of common 1,4-benzodiazepine drugs, Sister Chromatid Exchanges (SCEs) were employed, and for the determination of cytostaticity the Proliferation Rate Index (PRI) on lymphocytes of human whole blood cultures was estimated. It was found that benzodiazepines 3a, 3c, and 3e exhibit significant cytoprotection, but mild cytostatic effect (a statistically significant reduction of SCEs and a confined decrease of PRI values at similar concentrations). The most active compound was found to be 3e. [Display omitted] •Synthesis of new 2-aryloxymethylene-4-oxo-1,5-benzodiazepines.•Microwave assisted reaction of o-phenylenediamines with acetonedicarboxylates.•Structural assignments have been unambiguously achieved.•Study of cytogenetic activity in vitro.•Sister Chromatid Exchanges (SCEs) and Proliferation Rate Index were employed.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2013.06.028