Biology subjects

Sobreira Galdino, A.

Publications and source records attributed to Sobreira Galdino, 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↗

bioRxiv2024

Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products: pH-dependent inhibition explored through computer-aided drug design.

Visceral Leishmaniasis (VL) is a serious public health issue, documented in more than ninety countries, where an estimated 500,000 new cases emerge each year. Regardless of novel methodologies, advancements, and experimental interventions, therapeutic limitations, and drug resistance are still challenging. For this reason, based on previous research, we screened natural products (NP) from Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBEDB), Mexican Compound Database of Natural Products (BIOFACQUIM), and Peruvian Natural Products Database (PeruNPDB) databases, in addition to structural analogs of Miglitol and Acarbose, which have been suggested as treatments for VL and have shown encouraging action against parasites N-glycan biosynthesis. Using computer-aided drug design (CADD) approaches, the inhibitory effect of these NP candidates was evaluated by inhibiting the Mannosyl-oligosaccharide Glucosidase Protein (MOGS) from Leishmania infantum, an enzyme essential for the protein glycosylation process, at various pH to mimic the parasites changing environment. Also, computational analysis was used to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profile, while molecular dynamic simulations were used to gather information on the interactions between these ligands and the protein target. Our findings indicated that Ocotillone and Subsessiline have potential antileishmanial effects at pH 5 and 7, respectively, due to their high binding affinity to MOGS and interactions in the active center. Furthermore, these compounds were non-toxic and had the potential to be administered orally. This research indicates the promising anti-leishmanial activity of Ocotillone and Subsessiline, suggesting further validation through in vitro and in vivo experiments.

bioinformatics↗