In vitro evaluation of cytotoxicity and leishmanicidal activity of phthalimido-thiazole derivatives

Aliança, Amanda Silva dos Santos; Oliveira, Arsênio Rodrigues; Feitosa, Ana Paula Sampaio; Ribeiro, Karla Raíza Cardoso; Castro, Maria Carolina Accioly Brelaz de; Leite, Ana Cristina Lima; Alves, Luíz Carlos; Brayner, Fábio André

doi:10.1016/j.ejps.2017.05.005

Cited by 40 publications

(18 citation statements)

References 31 publications

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“…Previous studies have shown that 1,3-thiazole derivatives have leishmanicidal activity 26 and that phthalimide-thiazole derivatives have higher affinity to L. infantum FeSOD than human CuZnSOD 27 . These results suggest the thiazole ring is a suitable scaffold upon which novel SOD inhibitors might be developed.…”

Section: Resultsmentioning

confidence: 92%

Synthesis and biological evaluation of thiazole derivatives as LbSOD inhibitors

Brito

Silva

Brondani³

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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Leishmaniasis is considered as one of the major neglected tropical diseases due to its magnitude and wide geographic distribution. Leishmania braziliensis, responsible for cutaneous leishmaniasis, is the most prevalent species in Brazil. Superoxide dismutase (SOD) belongs to the antioxidant pathway of the parasites and human host. Despite the differences between SOD of Leishmania braziliensis and human make this enzyme a promising target for drug development efforts. No medicinal chemistry effort has been made to identify LbSOD inhibitors. Herein, we show that thermal shift assays (TSA) and fluorescent protein-labeled assays (FPLA) can be employed as primary and secondary screens to achieve this goal. Moreover, we show that thiazole derivatives bind to LbSOD with micromolar affinity.

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Section: Resultsmentioning

confidence: 92%

Synthesis and biological evaluation of thiazole derivatives as LbSOD inhibitors

Brito

Silva

Brondani³

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Brito et al [185], based on previous studies on the leishmanicidal activity of 1,3 thiazole derivatives [186] and that phthalimide-thiazole derivatives showed higher af finity to L. infantum FeSOD than human CuZnSOD [187], designed a series of 2,4 subst tuted thiazole derivatives in order to evaluate their LbSOD inhibitory activity. Com pounds were tested using thermal shift assay (TSA) as well as fluorescent protein labeled assays (FLPA).…”

Section: Neglected Diseasesmentioning

confidence: 99%

Thiazole Ring—A Biologically Active Scaffold

2021

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Background: Thiazole is a good pharmacophore nucleus due to its various pharmaceutical applications. Its derivatives have a wide range of biological activities such as antioxidant, analgesic, and antimicrobial including antibacterial, antifungal, antimalarial, anticancer, antiallergic, antihypertensive, anti-inflammatory, and antipsychotic. Indeed, the thiazole scaffold is contained in more than 18 FDA-approved drugs as well as in numerous experimental drugs. Objective: To summarize recent literature on the biological activities of thiazole ring-containing compounds Methods: A literature survey regarding the topics from the year 2015 up to now was carried out. Older publications were not included, since they were previously analyzed in available peer reviews. Results: Nearly 124 research articles were found, critically analyzed, and arranged regarding the synthesis and biological activities of thiazoles derivatives in the last 5 years.

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“…The proper maintenance of the mitochondrial membrane potential is essential for cell survival, since it it associated to the function of mitochondria. Furthermore, trypanosomatids have a single mitochondrion, which makes this organelle a potential target for drugs (Vannier-Santos et al, 2012;Aliança et al, 2017). In the present study, different than amphotericin B, LASSBio-1386 incubation did not result in depolarization of mitochondrial membrane potential of the parasite, suggesting that the compound cause the death of parasites by another biochemical pathway.…”

Section: Discussionmentioning

confidence: 46%

“…Methanol was used as a positive control. After incubation, data acquisition was performed using a LSRFortessa flow cytometer and the analysis was performed by FlowJo software (Aliança et al, 2017).…”

Section: Mitochondrial Membrane Potential Of Promastigotes Of L Amazmentioning

confidence: 99%

In Vitro, In Vivo and In Silico Effectiveness of LASSBio-1386, an N-Acyl Hydrazone Derivative Phosphodiesterase-4 Inhibitor, Against Leishmania amazonensis

et al. 2020

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Leishmaniasis are group of neglected diseases with worldwide distribution that affect about 12 million people. The current treatment is limited and may cause severe adverse effects, and thus, the search for new drugs more effective and less toxic is relevant. We have previously investigated the immunomodulatory effects of LASSBio-1386, an N-acylhydrazone derivative. Here we investigated the in vitro and in vivo activity of LASSBio-1386 against L. amazonensis. LASSBio-1386 inhibited the proliferation of promastigotes of L. amazonensis (EC50 = 2.4 ± 0.48 µM), while presenting low cytotoxicity to macrophages (CC50 = 74.1 ± 2.9 µM). In vitro incubation with LASSBio-1386 reduced the percentage of Leishmania-infected macrophages and the number of intracellular parasites (EC50 = 9.42 ± 0.64 µM). Also, in vivo treatment of BALB/c mice infected with L. amazonensis resulted in a decrease of lesion size, parasitic load and caused histopathological alterations, when compared to vehicle-treated control. Moreover, LASSBio-1386 caused ultrastructural changes, arrested cell cycle in G0/G1 phase and did not alter the membrane mitochondrial potential of L. amazonensis. Aiming to its possible molecular interactions, we performed docking and molecular dynamics studies on Leishmania phosphodiesterase B1 (PDB code: 2R8Q) and LASSBio-1386. The computational analyses suggest that LASSBio-1386 acts against Leishmania through the modulation of leishmanial PDE activity. In conclusion, our results indicate that LASSBio-1386 is a promising candidate for the development of new leishmaniasis treatment.

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In vitro evaluation of cytotoxicity and leishmanicidal activity of phthalimido-thiazole derivatives

Cited by 40 publications

References 31 publications

Synthesis and biological evaluation of thiazole derivatives as LbSOD inhibitors

Synthesis and biological evaluation of thiazole derivatives as LbSOD inhibitors

Thiazole Ring—A Biologically Active Scaffold

In Vitro, In Vivo and In Silico Effectiveness of LASSBio-1386, an N-Acyl Hydrazone Derivative Phosphodiesterase-4 Inhibitor, Against Leishmania amazonensis

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