Pharmacology, Toxicology and Pharmaceutics, Drug Discovery
23
Scopus Publications
Scopus Publications
Evaluation of phenyl hydrazide-based compounds as myeloperoxidase inhibitors Laryssa C. C. L. Salema, André B. Farias, Tiago R. Navarro, Patrick P. Pimentel, Thuany B. S. Aguiar, Nelilma C. Romeiro, Evanoel C. de Lima, Juliana M. Raimundo, Leandro L. da Silva Naunyn Schmiedeberg S Archives of Pharmacology, 2026 Myeloperoxidase (MPO) has been associated with a broad range of chronic inflammatory diseases since activated MPO catalyzes the production of HOCl, triggering both oxidative stress and inflammation. Since benzohydrazides are known as MPO inhibitors, a series of six N '-phenylbenzohydrazides and one quinazolin-4(3 H )-one analogue was evaluated through in vitro assays to measure inhibition of MPO, superoxide dismutase (SOD), and catalase (CAT) activities, as well as DPPH and superoxide-scavenging effects. Pharmacokinetic parameters of the compounds were evaluated in silico , and molecular docking studies were performed to predict their binding modes with the catalytic site of MPO. All phenylbenzohydrazides exhibited potent inhibitory effect on MPO activity, with four of them presenting IC 50 values below 0.5 μM. Bromine substitution, as in 2b , 2e , and 2f , enhanced the binding affinity to the active site of MPO, resulting in high inhibitory potency. In concentrations as high as 50 μM, compounds did not inhibit SOD activity but showed some inhibitory activity over CAT. Except for compound 2c , the phenylbenzohydrazides can scavenge DPPH radical, while only 2e can sequester superoxide anion. Quinazolin-4(3 H )-one analogue 3 , obtained from phenylbenzohydrazide 2a showed a more selective profile towards MPO compared to CAT but antioxidant activity was not observed. Phenylbenzohydrazide 2e is a potent MPO inhibitor with antioxidant properties, demonstrated through DPPH and superoxide anion scavenging, with high predicted gastrointestinal absorption. The results obtained in this study with N ’-phenylbenzohydrazides highlight the importance of structural modifications to improve the pharmacological profile of phenylhydrazides, contributing to the development of new anti-inflammatory drugs.
Preparation and characterization of chitosan and Aloe vera blends by co-precipitation for potential biomedical applications Pâmella Rayo de Luar Campos Gonçalves, Paloma Souza, Marina Cardoso Nemitz, Mario Sergio Schultz, Leandro Louback da Silva, Amanda Ribeiro Guimarães, Cicero Wellington Brito Bezerra Journal of Bioactive and Compatible Polymers, 2025 Blends of chitosan and Aloe vera exudate in ratios of 75:25, 50:50, and 25:75 were prepared from aqueous solutions using the co-precipitation technique. This method offers notable advantages including simplicity, rapid processing, and efficient separation of interacting phases from non-associated components, resulting in products with greater purity and compositional control. Samples and precursors were characterized using Fourier-transform infrared spectroscopy (FTIR), thermal analysis (TG/DTG), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS), swelling degree, antioxidant activity, and cell viability assay. The analyses indicated interactions between the biomaterials within the blend. Additionally, the biomaterials were found to be non-toxic, and the addition of Aloe vera exudate enhanced fibroblast cell viability. These findings underscore the significant potential of these biocompatible, antioxidant-rich blends, sustainably produced from renewable resources for a wide range of biotechnology applications.
Potential of Essential Oils from Cymbopogon winterianus Jowitt: Promising Evaluation for the Control of Mollusks and Embryos of Biomphalaria glabrata and Schistosoma mansoni Cercariae Keyla Nunes Farias Gomes, Francisco Paiva Machado, Ester Maria Mota, Ana Cláudia Rodrigues da Silva, Mikaella Gonçalves Xavier, Joana Tostes da Cunha e Menezes, Anita Ferreira do Valle, Leandro Louback da Silva, Beatriz de Frias Leite, Leandro Rocha, Robson Xavier Faria Pharmaceuticals, 2025 Background/objectives: Schistosomiasis is a parasitic disease that represents a serious public health problem. An alternative for the control of snails, intermediate hosts of schistosomiasis, is the use of molluskicides. Niclosamide, recommended by the WHO, has limitations, such as environmental toxicity, which has driven the search for safer and biodegradable alternatives, especially of plant origin. In this context, this study investigated the biological activity of Cymbopogon winterianus essential oil on embryos, juveniles, and adults of Biomphalaria glabrata and cercariae of Schistosoma mansoni. Methods: Essential oils (EOs) were extracted from fresh leaves via the Clevenger system and characterized via gas chromatography (GC/MS and GC/FID), revealing geraniol (25.0%), citronellal (29.2%), citronellol (10.5%) and elemol (9.6%) as the main components. Results: The results revealed lethal concentrations 90 (LC90) for young and adult snails of 60.72 mg/L, 74.21 mg/L and 115.35 mg/L, respectively. In the histological analysis, no changes were observed in the tissues of the mollusks exposed to the lethal concentration 25 (LC25). However, the lethal concentrations 50 (LC50) and 75 (LC75) caused crystalline concretions in proximity to the renal saccular portion. At a concentration of 60 mg/L, the oil resulted in 100% lethality in embryos and cercaricidal activity greater than 90% in 3 h. Acute toxicity tests in mice via the intraperitoneal or oral route did not reveal toxic effects, with hematological and biochemical parameters within the reference values. Furthermore, the oil did not inhibit acetylcholinesterase (AChE), indicating low toxicity to fish, and caused a slight reduction in human butyrylcholinesterase (hBChE) activity without affecting human AChE, which suggests low toxicity to mammalian tissues. In terms of environmental impact, the oil was not toxic to algae until the 75th day, with mortality observed thereafter. Conclusions: These results indicate that essential oils have great potential as biodegradable and safe alternatives for controlling mollusks and interrupting the schistosomiasis cycle.
Synthesis, in silico, and in vitro evaluation of 7-chloro-quinolines designed as myeloperoxidase inhibitors Gabriel Rodrigues Coutinho Pereira, Letícia de Souza Fraga, Romulo Pereira de Jesus, Rafael Compan Queiroz, Beatriz de Frias Leite, Marina Amaral Alves, Joelma Freire de Mesquita, Alessandra Mendonça Teles de Souza, Leandro Louback da Silva, Carlos Rangel Rodrigues, Lucio Mendes Cabral, Barbara de Azevedo Abrahim-Vieira, Maria Leticia de Castro Barbosa Journal of Molecular Structure, 2024
Pharmacological potential of 4-dimethylamino chalcone against acute and neuropathic pain in mice Isabela Souza dos Santos Marchon, Evelynn Dalila do Nascimento Melo, Mirella da Costa Botinhão, Greice Nascimento Pires, João Vitor Rocha Reis, Rodrigo Octavio Mendonça Alves de Souza, Ivana Correa Ramos Leal, André Gustavo Calvano Bonavita, Henrique Rocha Mendonça, Michelle Frazão Muzitano, Leandro Louback da Silva, Paula Lima do Carmo, Juliana Montani Raimundo Journal of Pharmacy and Pharmacology, 2024 Objectives This work investigated the acute antinociceptive effect of a synthetic chalcone, 4-dimethylamino chalcone (DMAC), as well as its effects on vincristine-induced peripheral neuropathy (VIPN) in mice. Methods The inhibitory activity of myeloperoxidase was assessed by measuring HOCl formation. Formalin and hot plate tests were used to study the acute antinociceptive effect of DMAC. VIPN was induced through the administration of vincristine sulphate (0.1 mg/kg, i.p., 14 days). Then, DMSO, DMAC (10 or 30 mg/kg; i.p.), or pregabalin (10 mg/kg, i.p.) were administered for 14 consecutive days. Thermal hyperalgesia and mechanical allodynia were evaluated before and after VIPN induction and on days 1, 3, 7, and 14 of treatment. Neurodegeneration and neuroinflammation were assessed through immunohistochemistry for NF200, iNOS, and arginase-1 within the sciatic nerve. Key findings DMAC inhibited myeloperoxidase activity in vitro and presented an acute antinociceptive effect in both formalin and hot plate tests, with the involvement of muscarinic and opioid receptors. Treatment with 30 mg/kg of DMAC significantly attenuated thermal hyperalgesia and mechanical allodynia and prevented macrophage proinflammatory polarisation in VIPN mice. Conclusions Our results show that DMAC, acting through different mechanisms, effectively attenuates VIPN.
Ethyl acetate fraction and isolated phenolics derivatives from mandevilla moricandiana identified by uhplc-dad-esi-msn with pharmacological potential for the improvement of obesity-induced endothelial dysfunction Leticia L. D. M. Ferreira, Valéria de F. Leão, Cinthya M. de Melo, Thelma de B. Machado, Ana Claudia F. Amaral, Leandro L. da Silva, Naomi K. Simas, Michelle F. Muzitano, Ivana C. R. Leal, Juliana M. Raimundo Pharmaceutics, 2021 Endothelial dysfunction in obesity plays a key role in the development of cardiovascular diseases, and it is characterized by increased vascular tonus and oxidative stress. Thus, this study aimed to investigate the vasodilatory and antioxidant activities of Mandevilla moricandiana ethyl acetate fraction and subfractions. Vascular effects were investigated on aorta isolated from control and monosodium glutamate (MSG) induced-obese Wistar rats, and antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) methods. The ethyl acetate fraction (MMEAF) induced a concentration-dependent vasodilation on aortic rings through the NO pathway, with the involvement of histamine H1 and estrogen ERα receptors and showed potent antioxidant activity. In aorta of MSG obese rats, maximal relaxation to acetylcholine was increased in the presence of MMEAF (3 µg/mL), indicating that MMEAF ameliorated obesity-induced endothelial dysfunction. Quercetin and kaempferol aglycones and their correspondent glycosides, as well as caffeoylquinic acid derivatives, A-type procyanidin trimer, ursolic and oleanolic triterpenoid acids were identified in subfractions from MMEAF and seem to be the metabolites responsible for the vascular and antioxidant activities of this fraction.
A combined injectable contraceptive improves plasma redox status and does not induce vascular changes in female rats LUDMILLA C. DO ESPÍRITO SANTO NERY, LESLIE C.S. BRAZ, LETICIA L.D.M. FERREIRA, FLÁVIA P. VIEIRA, LEANDRO L. DA SILVA, HELENE N.H. BLANC, JULIANA M. RAIMUNDO Anais Da Academia Brasileira De Ciencias, 2021 This study aimed to investigate the effects of the combined injectable contraceptive (CIC) containing estradiol valerate (EV) and norethisterone enanthate (NET-EN) on aorta function and morphology, as well as on redox status, of female Wistar rats. Female rats (9-10 weeks of age) received intramuscular injections of CIC (0.1 mg EV plus 1 mg NET-EN) or castor oil (control group, CTL) for 8 weeks, once a week. Food intake, body weight and systolic blood pressure were measured during the treatment period. Thoracic aortic segments were prepared for isometric tension recording and morphological analysis. Redox status was evaluated by total oxidant status (TOS) and lipid peroxidation (LP) on plasma and reduced glutathione (GSH) on whole blood. CIC group presented lower food intake and lower total weight gain compared to CTL group. There was no change in systolic blood pressure, vascular response of aorta to phenylephrine and acetylcholine and aorta thickness. Plasma TOS and LP values were reduced in CIC group, although GSH was not altered. It was shown that the long-term treatment with the CIC containing EV plus NET-EN does not induce endothelial dysfunction and histomorphometric changes of vascular wall, as well as improves redox status on female Wistar rats.
Effects of bisphenol A and S on blood coagulation: in vivo, in vitro and in silico approaches in toxicodynamic Artur Paes Chagas, Beatriz Pereira Peixoto, Bianca Barros da Costa, Thamyris Almeida Moreira, Leonardo Paes Cinelli, Leandro Louback da Silva, Leandro Miranda-Alves, Clemilson Berto-Junior Toxicology Mechanisms and Methods, 2021 Bisphenol A (BPA) is a well-known endocrine disruptor with several effects on mammalian systems and has been linked to diseases, such as cancer. Bisphenol S (BPS) emerged as a likely alternative to BPA in industrial production. Despite being well studied and exhibiting BPA-like toxic capacity, many effects are still being elucidated. The blood coagulation system is well controlled in an effort to minimize blood loss. To our knowledge, no study reported actions of bisphenols in this system. The aim of this work was to evaluate the effects of bisphenols on blood coagulation. Zebrafish were used to measure bleeding time. To assess possible mechanisms, platelet-rich plasma was incubated with both bisphenols in the presence of arachidonic acid. Prothrombin time (PT) and activated partial thromboplastin time (APTT) assays were performed in the presence of BPA and BPS. Alignment of human factor VII sequence was compared to zebrafish and docking simulations performed with FVIIa and bisphenols. An extended time was observed in BPA-treated but not BPS-treated animals in bleeding time; in PT, bisphenols showed no effect. APTT was increased in the highest concentration of bisphenols, with no effects in platelet aggregation, indicating interference with factor VII. Protein alignment showed that both proteins have well conserved residues, as those being required for interaction of FVIIa-BPA and FVIIa-BPS complexes, as shown in molecular docking. Taken together, these data show BPA and BPS as capable of interfering with the coagulation process via FVIIa.
Isolation and characterization of flavonoids from Tapirira guianensis leaves with vasodilatory and myeloperoxidase-inhibitory activities Laura L. Calassara, Shaft C. Pinto, Cecília P. M. Condack, Beatriz F. Leite, Ludmilla C. do E. S. Nery, Luzineide W. Tinoco, Fernando A. Aguiar, Ivana C. R. Leal, Samantha M. Martins, Leandro L. da Silva, Juliana M. Raimundo, Michelle F. Muzitano Natural Product Research, 2021 The aim of this study was to perform the isolation and characterization of vasodilatory flavonoids from Tapirira guianensis Aubl. (Annacardiaceae) leaves. In this context, ethyl acetate fraction (EA fraction) was obtained and subjected to fractionation batches by HSCCC affording: myricetin 3-O-α-L-rhamnopyranoside (myricitrin, 1); quercetin 3-O-(6”-O-galloyl)-β-D-galactopyranoside (2); quercetin 3-O-α-L-arabinofuranoside (avicularin, 3); and quercetin 3-O-α-L-rhamnopyranoside (quercitrin, 4). Myricitrin (1) induced a relaxation of 56.07 ± 13.04% at 300 μM (P < 0.05; n = 5), indicating that this flavonoid contributes to the vasodilatory activity of EA fraction. In addition, all EA fraction flavonoids were evaluated for their capacity of inhibiting myeloperoxidase activity and flavonoid (2) (IC50 1.0 ± 0.3 µM) was the strongest peroxidase inhibitor. In conclusion, it was possible to verify that myricitrin together with quercetin are mainly responsible for vasodilatory potential, besides flavonoid 2 for myeloperoxidase inhibition. Together these flavonoids seem to be responsible for Tapirira guianensis cardiovascular effects.
