In silico prediction of ADMET parameters and in vitro evaluation of antioxidant and cytotoxic activities promoted by indole-thiosemicarbazone compounds.

Cancer is a complex and multifactorial disease characterized by uncontrolled cell growth and is one of the main causes of death in the world. This work aimed to evaluate a small series of 10 different indole-thiosemicarbazone compounds as potential antitumor agents. This is a pioneering study. For this, the antioxidant and cytotoxic capacity against normal and tumor cells was evaluated. The results showed that the compounds were able to promote moderate to low antioxidant activity for the ABTS radical scavenging assay. ADMET in silico assays showed that the compounds exhibited good oral bioavailability. As for toxicity, they were able to promote low cytotoxicity against normal cells, in addition to not being hemolytic. The compounds showed promising in vitro antitumor activity against the T47D, MCF-7, Jurkat and DU-145 strains, not being able to inhibit the growth of the Hepg2 strain. Through this in vitro study, it can be concluded that the compounds are potential candidates for antitumor agents.

Preliminary evaluation of the toxicological, antioxidant and antitumor activities promoted by the compounds 2,4-dihydroxy-benzylidene-thiosemicarbazones an in silico, in vitro and in vivo study.

Thiosemicarbazones are promising classes of compounds with antitumor activity. For this study, six 2,4-dihydroxy-benzylidene-thiosemicarbazones compounds were synthesized. These compounds were submitted to different assays in silico, in vitro and in vivo to evaluate the toxicological, antioxidant and antitumor effects. The in silico results were evaluated by the SwissADME and pkCSM platforms and showed that all compounds had good oral bioavailability profiles. The in vitro and in vivo toxicity assays showed that the compounds showed low cytotoxicity against different normal cells and did not promote hemolytic effects. The single dose acute toxicity test (2000 mg/kg) showed that none of the compounds were toxic to mice. In in vitro antioxidant activity assays, the compounds showed moderate to low activity, with PB17 standing out for the ABTS radical capture assay. The in vivo antioxidant activity highlighted the compounds 1, 6 and 8 that promoted a significant increase in the concentration of liver antioxidant enzymes. Finally, all compounds showed promising antitumor activity against different cell lines, especially MCF-7 and DU145 lines, in addition, they inhibited the growth of sarcoma 180 at concentrations lower than 50 mg/kg. These results showed that the evaluated compounds can be considered as potential antitumor agents.

Evaluation of the hydroalcoholic extract of Clarisia racemosa as an antiparasitic agent: an in vitro approach.

Clarisia racemosa Ruiz & Pav is a neotropical species found in humid forests from southern Mexico to southern Brazil. There are few studies related to the ethnopharmacological use of C. racemosa. Our objective was to evaluate the hydroalcoholic extract of C. racemosa as a potential antiparasitic agent. For this, we performed in vitro assays against strains of Leishmania amazonensis, Trypanosoma cruzi, Plasmodium falciparum, and Schistosoma mansoni. At the same time, immunomodulatory activity tests were carried out. The results demonstrated that the extract was able to stimulate and activate immune cells. In preliminary antiparasitic tests, structural modifications were observed in the promastigote form of L. amazonensis and in adult worms of S. mansoni. The extract was able to inhibit the growth of trypomastigote form of T. cruzi and finally showed low antiparasitic activity against strains of P. falciparum. It is pioneering work and these results demonstrate that C. racemosa extract is a promising alternative and contributes to the arsenal of possible forms of treatment to combat parasites. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03799-2.

In vitro evaluation of antioxidant, cytotoxic, trypanocidal and antimicrobial activities of lignin obtained from Caesalpinia ferrea leaves and its use as an excipient in the release of oxacillin and fluconazole.

In this context, the objective of this work was to isolate an alkaline lignin from the leaves of C. ferrea, in addition to investigating different biological activities and its use in the production of releasing tablets in vitro. Initially, the analysis of the composition of the leaves was performed, the contents were: cellulose (33.09 ± 0.3 %), hemicellulose (25.13 ± 0.1 %), lignin (18.29 ± 0.1 %), extractives (17.28 ± 1.0 %) and ash (6.20 ± 0.1 %). The leaves were fractionated to obtain alkaline lignin. The yield of obtaining lignin was 80.12 ± 0.1 %. The obtained lignin was characterized by the techniques: elemental analysis, FTIR, UV/Vis, 2D-NMR, GPC, TGA/DTG, DSC and PY-GC/MS. The results showed that the lignin obtained is of the GSH type, of low molecular weight and thermally stable. The in vitro antioxidant activity was evaluated by different assays promoting results only for DPPH (559.9 ± 0.8 µg/mL) and ABTS (484.1 ± 0.1 µg/mL) being able to promote low antioxidant activity. In addition, it showed low cytotoxicity in normal mammalian cells and promising antitumor and trypanocidal activity. Regarding antimicrobial activity, it was able to inhibit the growth of a strain of Staphylococcus aureus resistant to methicillin, presenting MIC values equal to the standard antibiotic oxacillin. It was also able to inhibit a strain of Candida albicans HAM13 sensitive to fluconazole. In addition, lignin promoted a synergistic effect by promoting a decrease in MIC against these two strains evaluated. Finally, lignin proved to be an excipient with potential for controlled release of antimicrobials.

In vitro activity, ultrastructural analysis and in silico pharmacokinetic properties (ADMET) of thiazole compounds against adult worms of Schistosoma mansoni.

The present work aimed to carry out in vitro biological assays of thiazole compounds against adult worms of Schistosoma mansoni, as well as the in silico determination of pharmacokinetic parameters to predict the oral bioavailability of these compounds. In addition to presenting moderate to low cytotoxicity against mammalian cells, thiazole compounds are not considered hemolytic. All compounds were initially tested at concentrations ranging from 200 to 6.25 µM against adult worms of S. mansoni parasites. The results showed the best activity of PBT2 and PBT5 at a concentration of 200 µM, which caused 100% mortality after 3 h of incubation. While at 6 h of exposure, 100% mortality was observed at the concentration of 100 µM. Subsequent studies with these same compounds allowed classifying PBT5, PBT2, PBT6 and PBT3 compounds, which were considered active and PBT1 and PBT4 compounds, which were considered inactive. In the ultrastructural analysis the compounds PBT2 and PBT5 (200 µM) promoted integumentary changes with exposure of the muscles, formation of integumentary blisters, integuments with abnormal morphology and destruction of tubercles and spicules. Therefore, the compounds PBT2 and PBT5 are promising antiparasitics against S. mansoni.

Xylans extracted from branches and leaves of Protium puncticulatum: antioxidant, cytotoxic, immunomodulatory, anticoagulant, antitumor, prebiotic activities and their structural characterization.

This work aimed to isolate and characterize xylans from branches and leaves of Protium puncticulatum, in addition to evaluating its in vitro biological and prebiotic potential. The results showed that the chemical structure of the obtained polysaccharides is similar being classified as homoxylans. The xylans presented an amorphous structure, in addition to being thermally stable and presenting a molecular weight close to 36 g/mol. With regard to biological activities, it was observed that xylans were able to promote low antioxidant activity (< 50%) in the different assays evaluated. The xylans also showed no toxicity against normal cells, in addition to being able to stimulate cells of the immune system and showing promise as anticoagulant agents. In addition to presenting promising antitumor activity in vitro. In assays of emulsifying activity, xylans were able to emulsify lipids in percentages below 50%. Regarding in vitro prebiotic activity, xylans were able to stimulate and promote the growth of different probiotics. Therefore, this study, in addition to being a pioneer, contributes to the application of these polysaccharides in the biomedical and food areas. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03506-1.

Interaction study with DNA/HSA, anti-topoisomerase IIα, cytotoxicity and in vitro antiproliferative evaluations and molecular docking of indole-thiosemicarbazone compounds.

In this work we will discuss the antiproliferative evaluation and the possible mechanisms of action of indole-thiosemicarbazone compounds LTs with anti-inflammatory activity, previously described in the literature. In this perspective, some analyzes were carried out, such as the study of binding to human serum albumin (HSA) and to biological targets: DNA and human topoisomerase IIα (topo). Antiproliferative study was performed with DU-145, Jukart, MCF-7 and T-47D tumor lines and J774A.1, besides HepG2 macrophages and hemolytic activity. In the HSA interaction tests, the highest binding constant was 3.70 × 106 M-1, referring to LT89 and in the fluorescence, most compounds, except for LT76 and LT87, promoted fluorescent suppression with the largest Stern-Volmer constant for the LT88 3.55 × 104. In the antiproliferative assay with DU-145 and Jurkat strains, compounds LT76 (0.98 ± 0.10/1.23 ± 0.32 µM), LT77 (0.94 ± 0.05/1.18 ± 0.08 µM) and LT87 (0.94 ± 0.12/0.84 ± 0.09 µM) stood out, due to their IC50 values mentioned above. With the MCF-7 and T-47D cell lines, the lowest IC50 was presented by LT81 with values of 0.74 ± 0.12 µM and 0.68 ± 0.10 µM, respectively, followed by the compounds LT76 and LT87. As well as the positive control amsacrine, the compounds LT76, LT81 and LT87 were able to inhibit the enzymatic action of human Topoisomerase IIα.

In vitro evaluation of alkaline lignins as antiparasitic agents and their use as an excipient in the release of benznidazole.

The Amazon rainforest is considered the largest tropical timber reserve in the world. The management of native forests in the Amazon is one of the most sensitive geopolitical issues today, given its national and international dimension. In this work, we obtained and characterized physicochemical lignins extracted from branches and leaves of Protium puncticulatum and Scleronema micranthum. In addition, we evaluated in vitro its potential as an antioxidant, cytotoxic agent against animal cells and antiparasitic against promastigotes of Leishmania amazonensis, trypomastigotes of T. cruzi and against Plasmodium falciparum parasites sensitive and resistant to chloroquine. The results showed that the lignins obtained are of the GSH type and have higher levels of guaiacyl units. However, they show structural differences as shown by spectroscopic analysis and radar charts. As for biological activities, they showed antioxidant potential and low cytotoxicity against animal cells. Antileishmanial/trypanocidal assays have shown that lignins can inhibit the growth of promastigotes and trypomastigotes in vitro. The lignins in this study showed low anti-Plasmodium falciparum activity against susceptible strains of Plasmodium falciparum and were able to inhibit the growth of the chloroquine-resistant strain. And were not able to inhibit the growth of Schistosoma mansoni parasites. Finally, lignins proved to be promising excipients in the release of benznidazole. These findings show the potential of these lignins not yet studied to promote different biological activities.

Biological activities and physicochemical characterization of alkaline lignins obtained from branches and leaves of Buchenavia viridiflora with potential pharmaceutical and biomedical applications.

In this work, we investigated in vitro different biological activities of alkaline lignins extracted from the species Buchenavia viridiflora, a tree from the Amazon rainforest used as a wood product. The chemical composition results for the twig and leaves were, respectively (%): cellulose (30.88 and 24. 28), hemicellulose (21.62 and 23.03), lignin (29.93 and 25.46), extractives (13.06 and 20.52), and ash (4.51 and 6.72). The yield was higher for the lignin of the branches (67.9 %) when compared to the leaves (60.2 %). Lignins are of the GSH type, low molecular weight and thermally stable. They promoted moderate to low antioxidant activity, highlighting the lignin of the branches, which presented an IC50 of 884.56 µg/mL for the DPPH assay and an IC50 of 14.08 µg/mL for ABTS. In the cytotoxicity assays, they showed low toxicity against macrophage cells (IC50 28.47 and 22.58 µg/mL). In addition, they were not cytotoxic against splenocytes and erythrocytes at concentrations ranging from 100 to 6.25 µg/mL. These were able to promote splenocyte proliferation and induce the production of anti-inflammatory cytokines. And inhibit the growth of tumor cells with IC50 ranging from 12.63 to values >100 µg/mL and microbial at a concentration of 512 µg/mL. Finally, they showed antiparasitic activity by inhibiting the growth of chloroquine-sensitive and resistant Plasmodium falciparum strains. These findings reinforce that the lignins in this study are promising for potential pharmaceutical and biomedical applications.

The genus Aeromonas: A general approach.

The genus Aeromonas comprises more than thirty Gram-negative bacterial species which mostly act as opportunistic microorganisms. These bacteria are distributed naturally in diverse aquatic ecosystems, where they are easily isolated from animals such as fish and crustaceans. A capacity for adaptation also makes Aeromonas able to colonize terrestrial environments and their inhabitants, so these microorganisms can be identified from different sources, such as soils, plants, fruits, vegetables, birds, reptiles, amphibians, among others. Infectious processes usually develop in immunocompromised humans; in fish and other marine animals this process occurs under conditions of stress. Such events are most often associated with incorrect practices in aquaculture. Aeromonas has element diverse ranges, denominated virulence factors, which promote adhesion, colonization and invasion into host cells. These virulence factors, such as membrane components, enzymes and toxins, for example, are differentially expressed among species, making some strains more virulent than others. Due to their diversity, no single virulence factor was considered determinant in the infectious process generated by these microorganisms. Unlike other genera, Aeromonas species are erroneously differentiated by conventional biochemical tests. Therefore, molecular assays are necessary for this purpose. Nevertheless, new means of identification have been considered in order to generate methods that, like molecular tests, can correctly identify these microorganisms. The main objectives of this review are to explain environmental and structural characteristics of the Aeromonas genus and to discuss virulence mechanisms that these bacteria use to infect aquatic organisms and humans, which are important aspects for aquaculture and public health, respectively. In addition, this review aims to clarify new tests for the precise identification of the species of Aeromonas, contributing to the exact and specific diagnosis of infections by these microorganisms and consequently the treatment.