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Review
. 2021 May 10;26(9):2796.
doi: 10.3390/molecules26092796.

Benzodiazepines: Drugs with Chemical Skeletons Suitable for the Preparation of Metallacycles with Potential Pharmacological Activity

Artur V da Silva  1 , Simoni M P Meneghetti  1 , Mario R Meneghetti  1
Affiliations
Review

Benzodiazepines: Drugs with Chemical Skeletons Suitable for the Preparation of Metallacycles with Potential Pharmacological Activity

Artur V da Silva et al. Molecules. .

Abstract

The synthesis of organometallic compounds with potential pharmacological activity has attracted the attention of many research groups, aiming to take advantage of aspects that the presence of the metal-carbon bond can bring to the design of new pharmaceutical drugs. In this context, we have gathered studies reported in the literature in which psychoactive benzodiazepine drugs were used as ligands in the preparation of organometallic and metal complexes and provide details on some of their biological effects. We also highlight that most commonly known benzodiazepine-based drugs display molecular features that allow the preparation of metallacycles via C-H activation. These organometallic compounds merit further attention regarding their potential biological effects, not only in terms of psychoactive drugs but also in the search for drug replacements, for example, for cancer treatments.

Keywords: benzodiazepines; biological activity; metallodrugs; organometallic complexes.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
General molecular structures of the most commercialized 1,4-benzodiazepines: ketone and triazole derivatives. The 1,4-benzodizapine core is highlighted in blue.
Figure 2
Figure 2
Some examples of BZDs that can be found on the market.
Figure 3
Figure 3
The fragments present in BZD drugs, derived from phenylmethanimine or pyridinylmethanimine, which are responsible for the reactivity of these compounds, leading to metal complexes via ortho-metallation or chelation.
Figure 4
Figure 4
Some examples of applied metallodrugs or those in the advanced trial stage.
Figure 5
Figure 5
A series of BZD-Au(I) derivatives prepared by Cinellu and coworkers (A–D).
Figure 6
Figure 6
Example of an insertion reaction of CO in the Pd-C bond of palladacycles derived from BZDs.
Figure 7
Figure 7
First example of organogold(I) derived from BZDs.
Figure 8
Figure 8
Organometallic compounds of ruthenium derived from BZDs (A,B).
Figure 9
Figure 9
First example of a metallacycle in which the benzodiazepine derivative acts as a pincer ligand.
Figure 10
Figure 10
Ortho-functionalization of cyclopalladated 5-phenyl-1,4-benzodiazepine.
See this image and copyright information in PMC

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