Pharmacophore-Based Virtual Screening of Alkaloids and Flavonoids for Designing Drugs with Inhibitory Activity on the Enzyme Monoamine Oxidase B Ana Carolina de Jesus Silva, Ana Beatriz Bezerra dos Santos, Mariana Pegrucci Barcelos, Carlos Henrique Tomich de Paula da Silva, Lorane Izabel da Silva Hage-Melim Applied Sciences Switzerland, 2025 Parkinson’s disease is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons, resulting in multiple motor and cognitive impairments. Among the hypotheses proposed for its etiology, oxidative stress mediated by the enzyme monoamine oxidase B (MAO-B) stands out, as it is directly associated with dopamine metabolism. In this context, the search for molecules with potential antiparkinsonian activity and low toxicity, particularly those of natural origin, has been extensively investigated using computational approaches. In the present study, a pharmacophore-based virtual screening was carried out on molecules belonging to the alkaloid and flavonoid groups, followed by the evaluation of their pharmacokinetic, toxicological, and biological activity profiles, as well as ligand–receptor interaction analysis through molecular docking. The results indicated that palmatine, genistein, ZINC00597214, and ZINC72342127 exhibited superior performance compared to the other analyzed structures, considering all evaluated criteria. Therefore, this study, through in silico methodologies, demonstrated the antiparkinsonian potential of several chemical structures, attributable to their inhibitory activity on the MAO-B enzyme. Further experimental investigations, both in vitro and in vivo, are necessary to more comprehensively characterize the properties of these molecules, with the ultimate goal of developing new therapeutic strategies for the treatment of Parkinson’s disease.
In silico Screening of Monamine Oxidase B Inhibitors for the Treatment of Central Nervous System Disorders Anderson L. P. da Costa, Henrique B. Lima, Ana C. J. Silva, Gabrieli S. Oliveira, Mariana P. Barcelos, et al. Journal of the Brazilian Chemical Society, 2025 Worldwide, millions of people suffer from neurological and psychiatric conditions, such as schizophrenia, depression, and neurodegenerative diseases. These conditions are often linked to hyperactivity of monoamine oxidase B (MAO-B) in the brain, and inhibiting this enzyme can reduce oxidative stress, stabilize neurotransmitter levels, and alleviate symptoms. In this context, a pharmacophoric model was created using PharmaGist with 31 hits extracted from BindingDB to enable a pharmacophoric-based search of potential MAO-B inhibitors in ZincPharmer’s chemical space, followed by the building of 10 conformers for each molecule in the software OMEGA, screening for structural and electrostatic similarity to safinamide using ROCS (Rapid overlay of chemical structures) and EON (Electrostatic similarity for lead-hopping), respectively. In addition, the molecular docking with Gold using the score function was performed to rank the ligands with the highest probabilities of affinity to MAO-B and then discriminate those with suitable physical-chemical, pharmacokinetic, and toxicological features using the tools QikProp, SwissADME, and DEREK. Four potential ligands with selective MAO-B inhibitor properties were identified, which show promise as future therapeutic agents for MAO-B-related disorders.
GDP-mannose pyrophosphorylase is an efficienttarget in Xanthomonas citri for citrus canker control André Vessoni Alexandrino, Mariana Pegrucci Barcelos, Leonardo Bruno Federico, Tamiris Garcia da Silva, Lúcia Bonci Cavalca, et al. Microbiology Spectrum, 2024 Xanthomonas citri subsp. citri (Xcc) is a bacterium that causes citrus canker, an economically important disease that results in premature fruit drop and reduced yield of fresh fruit. In this study, we demonstrated the involvement of XanB, an enzyme with phosphomannose isomerase (PMI) and guanosine diphosphate-mannose pyrophosphorylase (GMP) activities, in Xcc pathogenicity. Additionally, we found that XanB inhibitors protect the host against Xcc infection. Besides being deficient in motility, biofilm production, and ultraviolet resistance, the xanB deletion mutant was unable to cause disease, whereas xanB complementation restored wild-type phenotypes. XanB homology modeling allowed in silico virtual screening of inhibitors from databases, three of them being suitable in terms of absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties, which inhibited GMP (but not PMI) activity of the Xcc recombinant XanB protein in more than 50%. Inhibitors reduced citrus canker severity up to 95%, similarly to copper-based treatment. xanB is essential for Xcc pathogenicity, and XanB inhibitors can be used for the citrus canker control. IMPORTANCE Xcc causes citrus canker, a threat to citrus production, which has been managed with copper, being required a more sustainable alternative for the disease control. XanB was previously found on the surface of Xcc, interacting with the host and displaying PMI and GMP activities. We demonstrated by xanB deletion and complementation that GMP activity plays a critical role in Xcc pathogenicity, particularly in biofilm formation. XanB homology modeling was performed, and in silico virtual screening led to carbohydrate-derived compounds able to inhibit XanB activity and reduce disease symptoms by 95%. XanB emerges as a promising target for drug design for control of citrus canker and other economically important diseases caused by Xanthomonas sp.
Protein–Protein Interaction for Drug Discovery Beatriz Brambila, Ana Carolina F. S. Martelli, Mariana Pegrucci Barcelos, Solange Cristina Antão, Carlos H. T. P. da Silva, et al. Engineering Materials, 2024
Moonlighting Proteins: Importance and Current Scenarios Ana Carolina Franco Severo Martelli, Beatriz Brambila, Mariana Pegrucci Barcelos, Flávia da Silva Zandonadi, Solange Cristina Antão, et al. Engineering Materials, 2024
Chromatographic profile, in silico and in vivo study of the pharmacokinetic and toxicological properties of major constituent present in kefir, the kefiran Susy Érika de Lima Barros, Henrique Barros de Lima, Leandra Karoline Alves Gonçalves, Lenir Cabral Correia, Maiara de Fátima de Brito Brito, et al. Toxicology Research, 2022 Kefiran is a polysaccharide present in kefir grains that have been widely explored due to its potential health benefits. The objective of this work was to characterize and quantify the components present in the ethanolic extract of milk kefir grains; to study its pharmacokinetic and toxicological properties in silico and evaluate the acute toxicity of the kefiran in zebrafish. The prediction of pharmacokinetic properties was performed by QikProp software. In silico toxicity assessment was performed using the DEREK (deductive estimate of risk from existing knowledge) software. In the chromatographic, kefiran was identified as the major component. Results showed that the kefiran had low human oral absorption and intestinal absorption its due poor solubility profile; low logP value, indicating its lipophilicity and the low MDCK and Caco-2 cells permability, and unable to cross the blood–brain barrier. Kefiran did not present any structural warning for in silico toxicity. In zebrafish, the dose of 2,000 mg/kg of kefiran produced nonsignificant alterations in the analyzed organs. It can be said then that kefiran has an acceptable degree of safety for use in the development of drugs or functional foods. Further research such as in vivo testing to confirm its pharmacological potential is currently underway.
Lead Optimization in Drug Discovery Mariana Pegrucci Barcelos, Suzane Quintana Gomes, Leonardo Bruno Federico, Isaque Antonio Galindo Francischini, Lorane Izabel da Silva Hage-Melim, et al. Engineering Materials, 2022
Virtual Screening of Drug Candidates for Repositioning for the Treatment of Parkinson’s Disease ALP da Costa, HB Lima, MP Barcelos, CHT de Paula da Silva, ... Computational Intelligence in Drug Development, 1-26 , 2025 2025
Therapeutic Peptides: Innovation and Potential at the Frontier of Medicine and Pharmacology MP Barcelos, B Brambila, MTM Novo-Mansur, ... Computational Intelligence in Drug Development, 101-117 , 2025 2025
Enzymes as Targets for Disease Control: From Discovery to Application B Brambila, ACFS Martelli, AEM Rosa, MP Barcelos, SC Antão, ... Computational Intelligence in Drug Development, 127-147 , 2025 2025
Pharmacophore-Based Virtual Screening of Alkaloids and Flavonoids for Designing Drugs with Inhibitory Activity on the Enzyme Monoamine Oxidase B AC de Jesus Silva, ABB dos Santos, MP Barcelos, CHT de Paula da Silva, ... Applied Sciences 15 (18), 10162 , 2025 2025 Citations: 1
The Role of Artificial Intelligence in the Discovery of New Drugs MP Barcelos, CHT de Paula da Silva Progress in Hydrogen Energy, Fuel Cells, Nano-Biotechnology and Advanced … , 2024 2024
Herbal medicines: from history to current research—a comprehensive survey ACJ Silva, AV Fassio, MP Barcelos, LIS Hage-Melim Progress in Hydrogen Energy, Fuel Cells, Nano-Biotechnology and Advanced … , 2024 2024 Citations: 6
Antiallergic, Antioxidant, Anti-Inflammatory and Immunostimulant Potential of Kefiran Postbiotic: Molecular Docking, Prediction of Pharmacokinetic Properties and Biological … SÉL Barros, HB Lima, MA Batista, RAS Cruz, MP Barcelos, GM Silva, ... Progress in Hydrogen Energy, Fuel Cells, Nano-Biotechnology and Advanced … , 2024 2024 Citations: 2
Moonlighting proteins: importance and current scenarios ACFS Martelli, B Brambila, MP Barcelos, F da Silva Zandonadi, SC Antão, ... Progress in Hydrogen Energy, Fuel Cells, Nano-Biotechnology and Advanced … , 2024 2024 Citations: 1
In silico Screening of Monamine Oxidase B Inhibitors for the Treatment of Central Nervous System Disorders ALP Costa, HB Lima, ACJ Silva, GS Oliveira, MP Barcelos, CHTP Silva, ... Journal of the Brazilian Chemical Society 36 (4), e-20240192 , 2024 2024 Citations: 1
GDP-mannose pyrophosphorylase is an efficient target in Xanthomonas citri for citrus canker control AV Alexandrino, MP Barcelos, LB Federico, TG da Silva, LB Cavalca, ... Microbiology Spectrum 12 (6), e03673-23 , 2024 2024 Citations: 1
In Silico Approaches in Pesticides MP Barcelos, CHTP da Silva Trends and Innovations in Energetic Sources, Functional Compounds and … , 2023 2023
Protein–protein interaction for drug discovery B Brambila, ACFS Martelli, MP Barcelos, SC Antão, CHTP da Silva, ... Trends and Innovations in Energetic Sources, Functional Compounds and … , 2023 2023 Citations: 4
Lead optimization in drug discovery MP Barcelos, SQ Gomes, LB Federico, IAG Francischini, LIS Hage-Melim, ... Research topics in bioactivity, environment and energy: experimental and … , 2022 2022 Citations: 22
Ligand-based drug design for selection of molecules with pharmacological activity in essential tremor ACJ Silva, SQ Gomes, MP Barcelos, CHT de Paula da Silva, CA Taft, ... Research Topics in Bioactivity, Environment and Energy: Experimental and … , 2022 2022 Citations: 2
Pathophysiology, Molecular Interaction Mechanism, Metabolism, Pharmacotherapy and New Perspectives in the Pharmacological Treatment of Chemical Dependence on the Main Illicit … JV Ferreira, GA Chaves, MA Batista, LC Correia, LR Souza, DC Costa, ... Research Topics in Bioactivity, Environment and Energy: Experimental and … , 2022 2022
Structural aspects of organic compounds as proteasome inhibitors addressed to several diseases SQ Gomes, GM Silva, MP Barcelos, LIS Hage-Melim, ... Research Topics in Bioactivity, Environment and Energy: Experimental and … , 2022 2022 Citations: 3
How Basic Programming Knowledge can Help the Drug Discovery Process LB Federico, MP Barcelos, SQ Gomes, IIAG Francischini, ALP da Costa, ... Research Topics in Bioactivity, Environment and Energy: Experimental and … , 2022 2022
Chromatographic profile, in silico and in vivo study of the pharmacokinetic and toxicological properties of major constituent present in kefir, the kefiran SÉL Barros, HB de Lima, LKA Gonçalves, LC Correia, MFB Brito, ... Toxicology Research 11 (3), 520-528 , 2022 2022 Citations: 1
Potential colchicine binding site inhibitors unraveled by virtual screening, molecular dynamics and MM/PBSA LB Federico, GM Silva, SQ Gomes, IAG Francischini, MP Barcelos, ... Computers in Biology and Medicine 137, 104817 , 2021 2021 Citations: 27
Identification of known drugs as potential SARS-CoV-2 Mpro inhibitors using ligand-and structure-based virtual screening LB Federico, GM Silva, LI da Silva Hage-Melim, SQ Gomes, MP Barcelos, ... Future Medicinal Chemistry 13 (16), 1353-1366 , 2021 2021 Citations: 11
MOST CITED SCHOLAR PUBLICATIONS
Virtual screening, ADME/Tox predictions and the drug repurposing concept for future use of old drugs against the COVID-19 LI da Silva Hage-Melim, LB Federico, NKS de Oliveira, VCC Francisco, ... Life Sciences 256, 117963 , 2020 2020 Citations: 88
Antioxidant Effect of Flavonoids Present in Euterpe oleracea Martius and Neurodegenerative Diseases: A Literature Review NKS de Oliveira, MRS Almeida, FMM Pontes, MP Barcelos, ... Central Nervous System Agents in Medicinal ChemistryChemistry-Central … , 2019 2019 Citations: 56
Pharmacophore and structure-based drug design, molecular dynamics and admet/tox studies to design novel potential pad4 inhibitors MP Barcellos, CBR Santos, LB Federico, PF Almeida, CHTP da Silva, ... Journal of Biomolecular Structure and Dynamics 37 (4), 966-981 , 2019 2019 Citations: 53
Potential beneficial effects of kefir and its postbiotic, kefiran, on child food allergy SÉ de Lima Barros, C dos Santos Rocha, MSB de Moura, MP Barcelos, ... Food & function 12 (9), 3770-3786 , 2021 2021 Citations: 40
Potential colchicine binding site inhibitors unraveled by virtual screening, molecular dynamics and MM/PBSA LB Federico, GM Silva, SQ Gomes, IAG Francischini, MP Barcelos, ... Computers in Biology and Medicine 137, 104817 , 2021 2021 Citations: 27
Molecular docking, physicochemical properties, pharmacokinetics and toxicity of flavonoids present in Euterpe oleracea Martius NKS de Oliveira, MRS Almeida, FMM Pontes, MP Barcelos, GM Silva, ... Current Computer-Aided Drug Design 17 (4), 589-617 , 2021 2021 Citations: 25
Lead optimization in drug discovery MP Barcelos, SQ Gomes, LB Federico, IAG Francischini, LIS Hage-Melim, ... Research topics in bioactivity, environment and energy: experimental and … , 2022 2022 Citations: 22
Revisiting the proposition of binding pockets and bioactive poses for GSK-3β allosteric modulators addressed to neurodegenerative diseases GM Silva, RS Borges, KLB Santos, LB Federico, IAG Francischini, ... International Journal of Molecular Sciences 22 (15), 8252 , 2021 2021 Citations: 18
Vibration control of the set tower and wind turbine under the wind influence SM Avila, M Barcelos, M Morais, MAM Shzu, RC Silva 20th international congress of mechanical engineering COBEM , 2009 2009 Citations: 16
Allosteric modulators of potential targets related to Alzheimer's Disease: a Review GM Silva, MP Barcelos, JGC Poiani, LIS Hage‐Melim, CHTP da Silva ChemMedChem 14 (16), 1467-1483 , 2019 2019 Citations: 12
Identification of known drugs as potential SARS-CoV-2 Mpro inhibitors using ligand-and structure-based virtual screening LB Federico, GM Silva, LI da Silva Hage-Melim, SQ Gomes, MP Barcelos, ... Future Medicinal Chemistry 13 (16), 1353-1366 , 2021 2021 Citations: 11
Dynamic behavior analysis of wind turbine towers MVG Morais, M Barcelos, SM Avila, MAM Shzu, RC Silva Congreso de Métodos Numéricos en Ingeniera SEMNI, Barcelona, España , 2009 2009 Citations: 11
Herbal medicines: from history to current research—a comprehensive survey ACJ Silva, AV Fassio, MP Barcelos, LIS Hage-Melim Progress in Hydrogen Energy, Fuel Cells, Nano-Biotechnology and Advanced … , 2024 2024 Citations: 6
Key aspects for achieving hits by virtual screening studies LB Federico, MP Barcelos, GM Silva, IAG Francischini, CA Taft, ... Functional Properties of Advanced Engineering Materials and Biomolecules … , 2021 2021 Citations: 6
Periplasm-enriched fractions from Xanthomonas citri subsp. citri type A and X. fuscans subsp. aurantifolii type B present distinct proteomic profiles under in vitro … FS Zandonadi, SP Ferreira, AV Alexandrino, CM Carnielli, J Artier, ... Plos one 15 (12), e0243867 , 2020 2020 Citations: 6
Prediction of the Three-Dimensional Structure of Phosphate-6-mannose PMI Present in the Cell Membrane of Xanthomonas citri subsp. citri of Interest for the … MP Barcelos, LB Federico, CA Taft, CHT de Paula da Silva Emerging research in science and engineering based on advanced experimental … , 2020 2020 Citations: 5
Protein–protein interaction for drug discovery B Brambila, ACFS Martelli, MP Barcelos, SC Antão, CHTP da Silva, ... Trends and Innovations in Energetic Sources, Functional Compounds and … , 2023 2023 Citations: 4
Structural aspects of organic compounds as proteasome inhibitors addressed to several diseases SQ Gomes, GM Silva, MP Barcelos, LIS Hage-Melim, ... Research Topics in Bioactivity, Environment and Energy: Experimental and … , 2022 2022 Citations: 3
Antiallergic, Antioxidant, Anti-Inflammatory and Immunostimulant Potential of Kefiran Postbiotic: Molecular Docking, Prediction of Pharmacokinetic Properties and Biological … SÉL Barros, HB Lima, MA Batista, RAS Cruz, MP Barcelos, GM Silva, ... Progress in Hydrogen Energy, Fuel Cells, Nano-Biotechnology and Advanced … , 2024 2024 Citations: 2
Ligand-based drug design for selection of molecules with pharmacological activity in essential tremor ACJ Silva, SQ Gomes, MP Barcelos, CHT de Paula da Silva, CA Taft, ... Research Topics in Bioactivity, Environment and Energy: Experimental and … , 2022 2022 Citations: 2
