Evaluation of guanylhydrazone derivatives as inhibitors of Candida rugosa digestive lipase: Biological, biophysical, theoretical studies and biotechnological application

Santana, Camilla C.; Silva-Júnior, Edeildo Ferreira da; Santos, João César N.; Rodrigues, Érica Erlanny da Silva; Silva, Isabella M. da; Araújo-Júnior, João Xavier de; Nascimento, Ticiano Gomes do; Barbosa, Leandro A. Oliveira; Dornelas, Camila Braga; Figueiredo, Isis M.; Santos, Josué Carinhanha Caldas; Grillo, Luciano Aparecido Meireles

doi:10.1016/j.bioorg.2019.03.030

Cited by 21 publications

(10 citation statements)

References 58 publications

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“…All illustrations were generated by using PyMol ® software, v. 0.99 ( ). Lastly, all procedures performed in this study are in accordance with recently published works by our research team [ 94 , 95 , 96 , 97 , 98 , 99 , 100 ].…”

Section: Methodsmentioning

confidence: 92%

Computer-Aided Design, Synthesis, and Antiviral Evaluation of Novel Acrylamides as Potential Inhibitors of E3-E2-E1 Glycoproteins Complex from Chikungunya Virus

et al. 2020

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Chikungunya virus (CHIKV) causes an infectious disease characterized by inflammation and pain of the musculoskeletal tissues accompanied by swelling in the joints and cartilage damage. Currently, there are no licensed vaccines or chemotherapeutic agents to prevent or treat CHIKV infections. In this context, our research aimed to explore the potential in vitro anti-CHIKV activity of acrylamide derivatives. In silico methods were applied to 132 Michael’s acceptors toward the six most important biological targets from CHIKV. Subsequently, the ten most promising acrylamides were selected and synthesized. From the cytotoxicity MTT assay, we verified that LQM330, 334, and 336 demonstrate high cell viability at 40 µM. Moreover, these derivatives exhibited anti-CHIKV activities, highlighting the compound LQM334 which exhibited an inhibition value of 81%. Thus, docking simulations were performed to suggest a potential CHIKV-target for LQM334. It was observed that the LQM334 has a high affinity towards the E3-E2-E1 glycoproteins complex. Moreover, LQM334 reduced the percentage of CHIKV-positive cells from 74.07 to 0.88%, 48h post-treatment on intracellular flow cytometry staining. In conclusion, all virtual simulations corroborated with experimental results, and LQM334 could be used as a promising anti-CHIKV scaffold for designing new drugs in the future.

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Section: Methodsmentioning

confidence: 92%

Computer-Aided Design, Synthesis, and Antiviral Evaluation of Novel Acrylamides as Potential Inhibitors of E3-E2-E1 Glycoproteins Complex from Chikungunya Virus

et al. 2020

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“…The 1 H NMR spectra were obtained on a Bruker Avance 600 MHz spectrometer equipped with a 5 mm indirect detection probe ( Santana et al, 2019 ). The spectra were calibrated with internal standard TPMS.…”

Section: Methodsmentioning

confidence: 99%

“…Hydrogens atoms were added and water molecules were removed for the DNA structure. All of the DNA structure was selected (70 Å), and the ligands were docked using the Astex Statistical Potential (ASP) algorithm ( Lozano Untiveros et al, 2019 , Passos et al, 2020 , Santana et al, 2019 ). Finally, the optimal binding poses were selected for analysis and were chosen as the initial conformation for molecular dynamics (MD) simulations performed at 100 ns using the GROMACS® software program ( Braga et al, 2019 , Roque Marques et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

The new psychoactive substances 25H-NBOMe and 25H-NBOH induce abnormal development in the zebrafish embryo and interact in the DNA major groove

Barros

Nunes

Ribeiro

et al. 2021

Current Research in Toxicology

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“…All illustrations were generated by using PyMol ® software, v. 0.99 (https://pymol.org/2/). Lastly, all procedures performed in this study are in accordance with recently published works by our research team [43][44][45][46][47][48][49].…”

Section: Molecular Dockingmentioning

confidence: 99%

Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes

Aquino

França

Rodrigues

et al. 2022

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Background: Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most severe, fatal in 95% of cases. The undesired side-effects from first-line chemotherapy and the reported drug resistance search for effective drugs that can replace or supplement those currently used an urgent need. Aminoguanidine hydrazones (AGH's) have been explored for exhibiting a diverse spectrum of biological activities, in particular the antileishmanial activity of MGBG. The bioisosteres thiosemicarbazones (TSC's) offer a similar biological activity diversity, including antiprotozoal effects against Leishmania species and Trypanosoma cruzi. Objective: Considering the impact of leishmaniasis worldwide, this work aimed to design, synthesize, and perform a screening upon L. chagasi amastigotes and for the cytotoxicity of the small "in-house" library of both AGH and TSC derivatives and their structurally-related compounds. Method: A set of AGH's (3-7), TSC's (9, 10), and semicarbazones (11) were initially synthesized. Subsequently, different semi-constrained analogs were designed and also prepared, including thiazolidines (12), dihydrothiazines (13), imidazolines (15), pyrimidines (16, 18) azines (19, 20), and benzotriazepinones (23-25). All intermediates and target compounds were obtained with satisfactory yields and exhibited spectral data consistent with their structures. All final compounds were evaluated against L. chagasi amastigotes and J774.A1 cell line. Molecular docking was performed towards trypanothione reductase using GOLD® software. Result: The AGH's 3i, 4a, and 5d, and the TSC's 9i, 9k, and 9o were selected as valuable hits. These compounds presented antileishmanial activity compared with pentamidine, showing IC50 values ranged from 0.6 to 7.27 μM, maximal effects up to 55.3%, and satisfactory SI values (ranged from 11 to 87). On the other hand, most of the resulting semi-constrained analogs were found cytotoxic or presented reduced antileishmanial activity. In general, TSC class is more promising than its isosteric AGH analogs, and the beneficial aromatic substituent effects are not similar in both series. In silico studies have suggested that these hits are capable of inhibiting the trypanothione reductase from the amastigote forms. Conclusion: The promising antileishmanial activity of three AGH’s and three TSC’s was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 μM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are under progress, which will help to choose the best hits for in vivo experiments.

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Evaluation of guanylhydrazone derivatives as inhibitors of Candida rugosa digestive lipase: Biological, biophysical, theoretical studies and biotechnological application

Cited by 21 publications

References 58 publications

Computer-Aided Design, Synthesis, and Antiviral Evaluation of Novel Acrylamides as Potential Inhibitors of E3-E2-E1 Glycoproteins Complex from Chikungunya Virus

Computer-Aided Design, Synthesis, and Antiviral Evaluation of Novel Acrylamides as Potential Inhibitors of E3-E2-E1 Glycoproteins Complex from Chikungunya Virus

The new psychoactive substances 25H-NBOMe and 25H-NBOH induce abnormal development in the zebrafish embryo and interact in the DNA major groove

Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes

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