Biology subjects

Ferraz Coelho, E. A.

Publications and source records attributed to Ferraz Coelho, E. A..

3 recordsLinked to original sources

bioRxiv2024

Exploring the Potential of Malvidin and Echiodinin as Probable Antileishmanial Agents Through In Silico Analysis And In Vitro Efficacy

Leishmaniasis is a neglected tropical disease, caused by distinct Leishmania species, which have significant public health challenges due to treatment limitations such as toxicity, high cost, and drug resistance. This study explores the in vitro potential of Malvidin and Echioidinin as probable antileishmanial agents against Leishmania amazonensis, L. braziliensis, and L. infantum, comparing their efficacy to Amphotericin B (AmpB), a standard drug. Malvidin was more potent than Echioidinin across all parasite stages and species. For L. amazonensis, Malvidins inhibitory concentration (IC50) values were 197.71{+/-}17.20 {micro}M and 258.07{+/-}17 {micro}M (stationary and axenic amastigotes, respectively); whereas Echioidinin revealed IC50 values of 272.99{+/-}29.90 M and 335.96{+/-}19.35 M (stationary and axenic amastigotes, respectively). AmpB showed IC50 values of 0.06{+/-}0.01 {micro}M and 0.10{+/-}0.03 {micro}M, respectively. Malvidin demonstrated lower cytotoxicity activity in mammalian cells with a cytotoxic concentration (CC50) value of 2,920.31{+/-}80.29 {micro}M, while AmpBs showed a value of 1.06{+/-}0.12 {micro}M. Malvidin also exhibited favorable selectivity index (SI) values. Malvidin reduced infection rates by up to 35.75% in L. amazonensis-infected macrophages. In silico analysis uncovered strong binding interactions between Malvidin and enzyme arginase in the three species, with key residues such as HIS139 and PRO258 playing a crucial role. Tissue-specific markers expression analysis highlighted the potential Malvidins modulation of genes involved in oxidative stress and DNA repair, including glyoxalase 1 (GLO1) and apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1). The in vitro and in silico data corroborate the hypothesis that Malvidin is safe and can control the Leishmania parasites as a new natural compound for treatment. To further assess its therapeutic potential, in vivo studies are required to evaluate Malvidins efficacy, safety, and pharmacokinetics in animal models, which will be essential for validating its role as a candidate for leishmaniasis treatment.

bioinformatics↗

bioRxiv2024

Treatment options for Chagas Disease: a systematic review and meta-analysis applied to the preclinical studies using animal models

Chagas disease (CD) is a neglected tropical disease endemic to Latin America and has emerged as a global health concern due to the migration of infected individuals. With its epidemiological complexity, difficulty in obtaining appropriate diagnoses, and poor treatment, the search for novel therapeutic options remains. In this context, we conducted a systematic review and meta-analysis of preclinical studies employing animal models to verify the progress in CD treatment. We searched the PubMed database for CD treatment studies published between 1990 and 2023, adhering to the PRISMA guidelines. Twelve papers met the inclusion criteria. The findings indicate that the fifteen treatment alternatives examined, mainly between 2010 and 2014, demonstrated efficacy in experimental CD models, evidenced by significant parasitemia reduction. Bis-triazole DO870 and VNI were effective in the acute and chronic phases, respectively. However, of these emerging therapies, only posaconazole and fexinidazole have progressed to clinical trials, yielding unsatisfactory outcomes as CD monotherapies. This meta-analysis highlights the existence of promising new drug candidates for CD treatment, but most remain in the preclinical stages. Those that reached clinical trials did not demonstrate optimal results, underscoring the ongoing challenges in CD therapy. Collaborative efforts among the academic community, pharmaceutical industries, funding agencies, and government agencies are urgently needed to accelerate the development of more effective medications against CD.

pathology↗

bioRxiv2022

In silico-based screening for natural products structural analogs as new drugs candidate against leishmaniasis

Leishmaniasis is a disease with high mortality rates and approximately 1.5 million new cases each year. Despite the new approaches and advances to fight the disease, there are no effective therapies. Hence, this study aims to in silico screen for natural products structural analogs as new drugs candidate against leishmaniasis. We applied in silico analysis, such as virtual screening, molecular docking, molecular dynamics simulation, and Molecular Mechanics-Generalized Born Surface Area MM/GBSA estimation aiming to select structural analogs from natural products that have shown antileishmanial activity against arginase (ARG) enzyme and that could bind selectively against Leishmania ARG. The compounds 2H-1-Benzopyran, 3,4-dihydro-2-(2-methylphenyl)-(9CI), Echioidinin, and Malvidin showed good results against ARG targets from three parasite species and negative results for potential toxicities. The Malvidin ligand generated interactions in the active center at pH 2.0 conditions and hydrogen bonds enhancing receptor-ligand coupling. This work identified Malvidin as a potential drug candidate to treat leishmaniasis.

bioinformatics↗