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. 2023 Sep 28;16(10):1380.
doi: 10.3390/ph16101380.

First-Row Transition 7-Oxo-5-phenyl-1,2,4-triazolo[1,5-a]pyrimidine Metal Complexes: Antiparasitic Activity and Release Studies

Álvaro Martín-Montes  1 , Sandra Jimenez-Falcao  2 , Santiago Gómez-Ruiz  3 , Clotilde Marín  1 , José M Mendez-Arriaga  3
Affiliations

First-Row Transition 7-Oxo-5-phenyl-1,2,4-triazolo[1,5-a]pyrimidine Metal Complexes: Antiparasitic Activity and Release Studies

Álvaro Martín-Montes et al. Pharmaceuticals (Basel). .

Abstract

Leishmaniasis and Chagas disease are still considered neglected illnesses due to the lack of investment in research, despite the fact that almost one million new cases are reported every year. Four 7-oxo-5-phenyl-1,2,4-triazolo[1,5-a]pyrimidine (HftpO) first-row transition complexes (Cu, Co, Ni, Zn) have been studied for the first time in vitro against five different species of Leishmania spp. (L. infantum, L. braziliensis, L. donovani, L. peruviana and L. mexicana) as well as Trypanosoma cruzi, showing higher efficacy than the reference commercial drugs. UV and luminescence properties were also evaluated. As a proof of concept, anchoring of a model high-effective-metal complex as an antiparasitic agent on silica nanoparticles was carried out for the first time, and drug-release behaviour was evaluated, assessing this new approach for drug vehiculation.

Keywords: antiparasitic activity; coordination chemistry; drug release; leishmaniasis; metal complex; nanoparticles.

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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

Scheme 1
Scheme 1
HftpO derivative structure.
Figure 1
Figure 1
Perspective view of [Cu(ftpO)2(H2O)4] (1). Thermal ellipsoids are drawn at the 50% probability level. Reproduced with permission from [21], Elsevier, 2017.
Figure 2
Figure 2
Comparison between UV spectra of HftpO ligand and [M(ftpO)2(H2O)4] [M = Cu (1), Co (2), Ni (3), and Zn (4)] complexes in ethanol.
Figure 3
Figure 3
Comparison between UV spectra of MTL (grey), free HftpO (pink) and complex 1 (green). Only one complex spectrum is included in this comparison for simplicity, since the shape remains the same for the 4 metal complexes synthesized.
Figure 4
Figure 4
Comparison between the luminescent emission spectrum of free HftpO derivative (red) and its complexes 1,2 (yellow and blue, coincident), 3 (purple) and 4 (green).
Scheme 2
Scheme 2
Schematic procedure for the immobilization of HftpO and model CuftpO complex 1 onto the MSN surface.
Figure 5
Figure 5
MSN TEM micrography (left) and mean diameter size-distribution of MSN (right).
Figure 6
Figure 6
N2 adsorption/desorption isotherms of MSN (black) MSN-ftpO (pink) and MSN-CuftpO (green).
Figure 7
Figure 7
Kinetic release profile of the copper complex (1) from MSN-CuftpO. Data are shown only up to 3 h for simplicity.
Figure 8
Figure 8
Comparative SI values for Leishmania spp. strains between Glucantime, free HftpO ligand, and complexes 1–4.
Figure 9
Figure 9
Comparative SI values for Trypanosoma cruzi between benznidazole, free HftpO ligand, and complexes 1–4.
Figure 10
Figure 10
Comparative SI values for Leishmania infantum (left) and Leishmania braziliensis (right) between Glucantime (grey), MSN-ftpO (pink) and MSN-CuftpO (green).
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