Design, synthesis and biological evaluation of quinazoline derivatives as anti-trypanosomatid and anti-plasmodial agents

Mendoza-Martínez, César; Correa‐Basurto, José; Nieto-Meneses, Rocío; Márquez-Navarro, Adrián; Aguilar-Suárez, Rocío; Montero-Cortes, Miriam Dinora; Nogueda‐Torres, Benjamín; Suarez-Contreras, Erick; Galindo-Sevilla, Norma; Rojas-Rojas, Ángela; Rodriguez-Lezama, Alejandro; Hernández‐Luis, Francisco

doi:10.1016/j.ejmech.2015.04.028

Cited by 60 publications

(35 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The experimental data in this study permitted us to postulate that the optimized formulations are promising for the in vitro efficacy studies against the parasite, using the infected Vero cell model. This approach can make it possible to select the best candidates for the studies with animals and humans [ 47 , 48 , 49 ]. Regarding the possible administration routes, the passage of nanoemulsions by different gastrointestinal tract compartments, or dilution in the plasmatic circulation, for example, can change the droplet size and zeta potential, destabilizing the colloidal dispersion due to the changes in water amount, pH or composition of the medium [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading

Streck

Sarmento

Machado

et al. 2016

IJMS

View full text Add to dashboard Cite

Previous studies reported low benznidazole (BNZ) loading in conventional emulsions due to the weak interaction of the drug with the most common oils used to produce foods or pharmaceuticals. In this study, we focused on how the type of surfactant, surfactant-to-oil ratio w/w (SOR) and oil-to-water ratio w/w (OWR) change the phase behavior of different lipid-based drug delivery systems (LBDDS) produced by emulsion phase inversion. The surfactant mixture composed of soy phosphatidylcholine and sodium oleate (1:7, w/w, hydrophilic lipophilic balance = 16) stabilized medium chain triglyceride in water. Ten formulations with the clear aspect or less turbid dispersions (five with the SOR ranging from 0.5 to 2.5 and five with the OWR from 0.06 to 0.4) were selected from the phase behavior diagram to assess structural features and drug-loading capacity. The rise in the SOR induced the formation of distinct lipid-based drug delivery systems (nanoemulsions and liquid crystal lamellar type) that were identified using rheological measurements and cross-polarized light microscopy images. Clear dispersions of small and narrow droplet-sized liquid-like nanoemulsions, Newtonian flow-type, were produced at SOR from 0.5 to 1.5 and OWR from 0.12 to 0.4, while clear liquid or gel-like liquid crystals were produced at SOR from 1.5 to 2.5. The BNZ loading was improved according to the composition and type of LBDDS produced, suggesting possible drug location among surfactant layers. The cell viability assays proved the biocompatibility for all of the prepared nanoemulsions at SOR less than 1.5 and liquid crystals at SOR less than 2.5, demonstrating their promising features for the oral or parenteral colloidal delivery systems containing benznidazole for Chagas disease treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading

Streck

Sarmento

Machado

et al. 2016

IJMS

View full text Add to dashboard Cite

show abstract

“…Docking studies have been performed to pteridine reductase, followed by in vitro biological evaluation of the compounds. Quinazoline derivatives 38 presented low micromolar activity against pteridine reductase of T. cruzi, while three of the compounds under study exhibited better results than Nfx and Bzn, which were used as reference drugs [ 97 ].…”

Section: Drug Targets and Inhibitorsmentioning

confidence: 99%

An Overview on Target-Based Drug Design against Kinetoplastid Protozoan Infections: Human African Trypanosomiasis, Chagas Disease and Leishmaniases

et al. 2021

View full text Add to dashboard Cite

The protozoan diseases Human African Trypanosomiasis (HAT), Chagas disease (CD), and leishmaniases span worldwide and therefore their impact is a universal concern. The present regimen against kinetoplastid protozoan infections is poor and insufficient. Target-based design expands the horizon of drug design and development and offers novel chemical entities and potential drug candidates to the therapeutic arsenal against the aforementioned neglected diseases. In this review, we report the most promising targets of the main kinetoplastid parasites, as well as their corresponding inhibitors. This overview is part of the Special Issue, entitled “Advances of Medicinal Chemistry against Kinetoplastid Protozoa (Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp.) Infections: Drug Design, Synthesis and Pharmacology”.

show abstract

“…e Values obtained from the literature. 31 BZN, benznidazol; NFX, nifurtimox (reference drugs for the treatment of Chagas disease). The experiment was performed in triplicate, and cell growth was determined after 72 h of culture by counting viable forms.…”

Section: Acs Medicinal Chemistry Lettersmentioning

confidence: 99%

Discovery of a Biologically Active Bromodomain Inhibitor by Target-Directed Dynamic Combinatorial Chemistry

García

Alonso

Serra

et al. 2018

ACS Med. Chem. Lett.

View full text Add to dashboard Cite

Target-directed dynamic combinatorial chemistry (DCC) has emerged as a strategy for the identification of inhibitors of relevant therapeutic targets. In this contribution, we use this strategy for the identification of a high-affinity binder of a parasite target, the Trypanosoma cruzi bromodomain-containing protein TcBDF3. This protein is essential for viability of T. cruzi, the protozoan parasite that causes Chagas disease. A small dynamic library of acylhydrazones was prepared from aldehydes and acylhydrazides at neutral pH in the presence of aniline. The most amplified library member shows (a) high affinity for the template, (b) interesting antiparasitic activity against different parasite forms, and (c) low toxicity against Vero cells. In addition, parasites are rescued from the compound toxicity by TcBDF3 overexpression, suggesting that the toxicity of this compound is due to the TcBDF3 inhibition, i.e., the binding event that initially drives the molecular amplification is reproduced in the parasite, leading to selective toxicity.

show abstract

Design, synthesis and biological evaluation of quinazoline derivatives as anti-trypanosomatid and anti-plasmodial agents

Cited by 60 publications

References 32 publications

Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading

Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading

An Overview on Target-Based Drug Design against Kinetoplastid Protozoan Infections: Human African Trypanosomiasis, Chagas Disease and Leishmaniases

Discovery of a Biologically Active Bromodomain Inhibitor by Target-Directed Dynamic Combinatorial Chemistry

Contact Info

Product

Resources

About