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Highly selective and divergent syntheses, which are crucial in both organic synthesis and medicinal chemistry, involve significant advancements in compound accessibility. By modifying α-cyano esters into α-cyano ketones, the synthesis pathway broadens to include a diverse range of 4-CN, 5-amino, and 5-arylamino derivatives of 1,2,3-triazoles, which are achieved notably through the Dimroth rearrangement. This versatility extends further with the potential for a triple cascade reaction, leading to the production of carboximidamide compounds, which are facilitated by the Cornforth rearrangement. Advancements in compound accessibility not only expand the repertoire of synthesized molecules but also open new avenues for potential pharmacological agents. Building on these findings, we have developed an innovative and efficient method for the divergent synthesis of functionalized 1,2,3-triazoles. This method strategically utilizes α-cyanocarbonyls and arylazides by harnessing their reactivity and compatibility to orchestrate a variety of molecular transformations. By optimizing these substrates, our goal is to simplify synthetic routes, improve product yields, and accelerate the discovery and development of new chemical entities with promising biological activities.
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Aim: This work describes the synthesis and antimicrobial evaluation of 6-aminated 1,4-benzoquinones (6-AQs) against seven resistant pathogens.Materials & methods: The 6-AQs, synthesized via a Michael addition reaction between bromoquinone and p-substituted anilines, were assessed for their antimicrobial activity through both in vitro and in silico analyses.Results: Bromoquinone and 6-AQs with electron-withdrawing groups demonstrated activity against Pseudomonas aeruginosa, with minimum inhibitory concentrations ranging from 16 to 128 µg/ml, comparable to standard antimicrobials. Two derivatives exhibited minimum inhibitory concentrations values against methicillin-resistant Staphylococcus aureus ranging from 64 to 128 µg/ml. These compounds demonstrated both bacteriostatic and bactericidal effects, and antibiofilm features.Conclusion: The 6-AQs 19g and 19f showed a promising antimicrobial profile, indicating their potential as new therapeutic options.
[Box: see text].
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Since 1970 acyclovir (ACV) has been the reference drug in treating herpes simplex virus (HSV) infections. However, resistant herpes simplex virus type 1 (HSV-1) strains have emerged, narrowing the treatment efficacy. The antiviral activity of classical Na+, K+ ATPase enzyme (NKA) inhibitors linked the viral replication to the NKA's activity. Herein, we evaluated the anti-HSV-1 activity of synthetic naphthoquinones, correlating their antiviral activity with NKA inhibition. We tested seven synthetic naphthoquinones initially at 50 µM on HSV-1-infected African green monkey kidney cells (VERO cells). Only one compound, 2-hydroxy-3-(2-thienyl)-1,4-naphthoquinone (AN-06), exhibited higher antiviral activity with a low cytotoxicity. AN-06 reduced the viral titer of 9 (log10) to 1.32 (log10) and decreased the steps of attachment and penetration. The addition of AN-06 up to 20 h postinfection (hpi) interfered with the viral cycle. The viral infection alone increases NKA activity 3 h postinfection (hpi), scaling up to 6 hpi. The addition of AN-06 in a culture infected with HSV-1 decreased NKA activity, suggesting that its antiviral action is linked to NKA inhibition. Also, docking results showed that this compound binds at the same site of NKA in which adenosine triphosphate (ATP) binds. AN-06 exhibited promising pharmacokinetic and toxicology properties. Thus, we postulate that AN-06 may be a good candidate for antiviral compounds with a mechanism of action targeting NKA activity.
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BACKGROUND: This study investigates the potential of eleven 1H-1,2,3-triazol-1,4-naphthoquinone conjugates as virulence factor inhibitors (like Pyocyanin) and their affinity for PhzM, a crucial enzyme for Pyocyanin biosynthesis in Pseudomonas aeruginosa infections. METHODS: A straightforward synthetic pathway enabled the production of these compounds, which were characterized and structurally confirmed through spectroscopic analyses. Evaluation of their impact on PhzM thermal stability identified promising candidates for PhzM binders. RESULTS: Concentration-response behavior elucidated their binding affinity, revealing them as the first reported micromolar affinity ligands for PhzM. Structure-activity relationship analysis emphasized the role of specific molecular moieties in binding affinity modulation, paving the way for future advanced inhibitors' development. CONCLUSION: These findings highlight the potential of naphthoquinone-triazole derivatives as leads for novel therapeutics against P. aeruginosa infections.
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Antibacterianos , Testes de Sensibilidade Microbiana , Naftoquinonas , Pseudomonas aeruginosa , Piocianina , Triazóis , Naftoquinonas/farmacologia , Naftoquinonas/química , Naftoquinonas/síntese química , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Piocianina/antagonistas & inibidores , Piocianina/biossíntese , Piocianina/metabolismo , Relação Estrutura-Atividade , Triazóis/química , Triazóis/farmacologia , Triazóis/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Estrutura Molecular , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Humanos , Relação Dose-Resposta a DrogaRESUMO
We report the spatiotemporal increase in abundance of Anchoviella spp. (Engraulidae) through the diet of fish consumers after reservoir formation in the upper Tocantins River, Central Brazil. The increase in the abundance of this planktivorous fish evidences the growing importance of autochthonous herbivory food chains as the reservoir stabilized in this novel lentic ecosystem. These changes would otherwise remain unnoticed only through fish sampling, highlighting the importance of assessing trophic interactions to understand responses to damming at the community and ecosystem levels.
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Peixes , Cadeia Alimentar , Rios , Brasil , Animais , Dieta/veterinária , HerbivoriaRESUMO
BACKGROUND: Oral squamous cell carcinoma (OSCC) represents the primary form of oral cancer, posing a significant global health threat. The existing chemotherapy options are accompanied by notable side effects impacting patient treatment adherence. Consequently, the exploration and development of novel substances with enhanced anticancer effects and fewer side effects have become pivotal in the realms of biological and chemical science. OBJECTIVE: This work presents the pioneering examples of naphthoquinone-coumarin hybrids as a new category of highly effective cytotoxic substances targeting oral squamous cell carcinoma (OSCC). METHODS: Given the significance of both naphthoquinones and coumarins as essential pharmacophores/ privileged structures in the quest for anticancer compounds, this study focused on the synthesis and evaluation of novel naphthoquinones/coumarin hybrids against oral squamous cell carcinoma. RESULTS: By several in vitro, in silico, and in vivo approaches, we demonstrated that compound 6e was highly cytotoxic against OSCC cells and several other cancer cell types and was more selective than current chemotherapeutic drugs (carboplatin) and the naphthoquinone lapachol. Furthermore, compound 6e was non-hemolytic and tolerated in vivo at 50 mg/kg with an LD50 of 62.5 mg/kg. Furthermore, compound 6e did not induce apoptosis and cell cycle arrest but led to intracellular vesicle formation with LC3 aggregation in autophagosomes, suggesting an autophagic cell death. Additionally, 6e had a high-affinity potential for PKM2 protein, higher than the known ligands, such as lapachol or shikonin, and was able to inhibit this enzyme activity in vitro. CONCLUSION: We assert that compound 6e shows promise as a potential lead for a novel chemotherapeutic drug targeting OSCC, with potential applicability to other cancer types.
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Breast cancer stands as one of the foremost cause of cancer-related deaths globally, characterized by its varied molecular subtypes. Each subtype requires a distinct therapeutic strategy. Although advancements in treatment have enhanced patient outcomes, significant hurdles remain, including treatment toxicity and restricted effectiveness. Here, we explore the anticancer potential of novel 1,4-naphthoquinone/4-quinolone hybrids on breast cancer cell lines. The synthesized compounds demonstrated selective cytotoxicity against Luminal and triple-negative breast cancer (TNBC) cells, which represent the two main molecular types of breast cancer that depend most on cytotoxic chemotherapy, with potency comparable to doxorubicin, a standard chemotherapeutic widely used in breast cancer treatment. Notably, these derivatives exhibited superior selectivity indices (SI) when compared to doxorubicin, indicating lower toxicity towards non-tumor MCF10A cells. Compounds 11a and 11b displayed an improvement in IC50 values when compared to their precursor, 1,4-naphthoquinone, for both MCF-7 and MDA-MB-231 and a comparable value to doxorubicin for MCF-7 cells. Also, their SI values were superior to those seen for the two reference compounds for both cell lines tested. Mechanistic studies revealed the ability of the compounds to induce apoptosis and inhibit clonogenic potential. Additionally, the irreversibility of their effects on cell viability underscores their promising therapeutic utility. In 3D-cell culture models, the compounds induced morphological changes indicative of reduced viability, supporting their efficacy in a more physiologically relevant model of study. The pharmacokinetics of the synthesized compounds were predicted using the SwissADME webserver, indicating that these compounds exhibit favorable drug-likeness properties and potential as antitumor agents. Overall, our findings underscore the promise of these hybrid compounds as potential candidates for breast cancer chemotherapy, emphasizing their selectivity and efficacy.
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Antineoplásicos , Neoplasias da Mama , Naftoquinonas , Humanos , Naftoquinonas/farmacologia , Naftoquinonas/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Células MCF-7 , Quinolonas/farmacologia , Quinolonas/química , Apoptose/efeitos dos fármacos , Técnicas de Cultura de Células em Três Dimensões/métodos , Doxorrubicina/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacosRESUMO
Due to the growth in the number of patients and the complexity involved in anticancer therapies, new therapeutic approaches are urgent and necessary. In this context, compounds containing the selenium atom can be employed in developing new medicines due to their potential therapeutic efficacy and unique modes of action. Furthermore, tellurium, a previously unknown element, has emerged as a promising possibility in chalcogen-containing compounds. In this study, 13 target compounds (9a-i, 10a-c, and 11) were effectively synthesized as potential anticancer agents, employing a CuI-catalyzed Csp-chalcogen bond formation procedure. The developed methodology yielded excellent results, ranging from 30 to 85%, and the compounds were carefully characterized. Eight of these compounds showed promise as potential therapeutic drugs due to their high yields and remarkable selectivity against SCC-9 cells (squamous cell carcinoma). Compound 10a, in particular, demonstrated exceptional selectivity, making it an excellent choice for cancer cell targeting while sparing healthy cells. Furthermore, complementing in silico and molecular docking studies shed light on their physical features and putative modes of action. This research highlights the potential of these compounds in anticancer treatments and lays the way for future drug development efforts.
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The search for novel anticancer drugs is essential to expand treatment options, overcome drug resistance, reduce toxicity, promote innovation, and tackle the economic impact. The importance of these studies lies in their contribution to advancing cancer research and enhancing patient outcomes in the battle against cancer. Here, we developed new asymmetric hybrids containing two different naphthoquinones linked by a 1,2,3-1H-triazole nucleus, which are potential new drugs for cancer treatment. The antitumor activity of the novel compounds was tested using the breast cancer cell lines MCF-7 and MDA-MB-231, using the non-cancer cell line MCF10A as control. Our results showed that two out of twenty-two substances tested presented potential antitumor activity against the breast cancer cell lines. These potential drugs, named here 12g and 12h were effective in reducing cell viability and promoting cell death of the tumor cell lines, exhibiting minimal effects on the control cell line. The mechanism of action of the novel drugs was assessed revealing that both drugs increased reactive oxygen species production with consequent activation of the AMPK pathway. Therefore, we concluded that 12g and 12h are novel AMPK activators presenting selective antitumor effects.
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Antineoplásicos , Neoplasias da Mama , Naftoquinonas , Humanos , Feminino , Células MCF-7 , Espécies Reativas de Oxigênio/metabolismo , Triazóis/farmacologia , Naftoquinonas/farmacologia , Proteínas Quinases Ativadas por AMP , Proliferação de Células , Apoptose , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Leishmaniasis is a disease caused by Leishmania spp., affecting millions of people around the world. For decades, its treatment has been based on pentavalent antimonials, which notoriously cause toxic side effects in patients. In this study, epoxy-α-lapachone incorporated into an oil-in-water-type microemulsion (ELAP-ME) and meglumine antimoniate (MA) were assayed in monotherapy and in combination (ELAP-ME/MA) in BALB/c mice infected with Leishmania (Leishmania) amazonensis. In general, there was a reduction in paw lesion size (up to 37% reduction) and decreases of parasite loads in the footpad (â¼40%) and lymph nodes (â¼31%) of animals treated with ELAP-ME/MA, when compared to the non-treated control groups. Analyses of serum biochemical parameters revealed that the ELAP-ME/MA showed lower renal and hepatic toxicity when compared to MA 2-doses/week monotherapy. These findings indicate that the ELAP-ME/MA combination may be a promising approach for the treatment of cutaneous leishmaniasis.
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Antiprotozoários , Leishmania , Leishmaniose Cutânea , Naftoquinonas , Compostos Organometálicos , Humanos , Animais , Camundongos , Antimoniato de Meglumina/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Camundongos Endogâmicos BALB CRESUMO
Inferring causal relationships from observational data is a key challenge in understanding the interpretability of Machine Learning models. Given the ever-increasing amount of observational data available in many areas, Machine Learning algorithms used for forecasting have become more complex, leading to a less understandable path of how a decision is made by the model. To address this issue, we propose leveraging ensemble models, e.g., Random Forest, to assess which input features the trained model prioritizes when making a forecast and, in this way, establish causal relationships between the variables. The advantage of these algorithms lies in their ability to provide feature importance, which allows us to build the causal network. We present our methodology to estimate causality in time series from oil field production. As it is difficult to extract causal relations from a real field, we also included a synthetic oil production dataset and a weather dataset, which is also synthetic, to provide the ground truth. We aim to perform causal discovery, i.e., establish the existing connections between the variables in each dataset. Through an iterative process of improving the forecasting of a target's value, we evaluate whether the forecasting improves by adding information from a new potential driver; if so, we state that the driver causally affects the target. On the oil field-related datasets, our causal analysis results agree with the interwell connections already confirmed by tracer information; whenever the tracer data are available, we used it as our ground truth. This consistency between both estimated and confirmed connections provides us the confidence about the effectiveness of our proposed methodology. To our knowledge, this is the first time causal analysis using solely production data is employed to discover interwell connections in an oil field dataset.
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Algoritmos , Algoritmo Florestas Aleatórias , Fatores de Tempo , Causalidade , PrevisõesRESUMO
The subclass naphthoquinone represents a substance group containing several compounds with important activities against various pathogenic microorganisms. Accordingly, we evaluated O-allyl-lawsone (OAL) antiparasitic and antifungal activity free and encapsulated in 2-hydroxypropyl-ß-cyclodextrin (OAL MKN) against Trypanosoma cruzi and Sporothrix spp. OAL and OAL MKN were synthesized and characterized by physicochemical methods. The IC50 values of OAL against T. cruzi were 2.4 µM and 96.8 µM, considering epimastigotes and trypomastigotes, respectively. At the same time, OAL MKN exhibited a lower IC50 value (0.5 µM) for both trypanosome forms and low toxicity for mammalian cells. Additionally, the encapsulation showed a selectivity index approximately 240 times higher than that of benznidazole. Regarding antifungal activity, OAL and OAL MKN inhibited Sporothrix brasiliensis growth at 16 µM, while Sporothrix schenckii was inhibited at 32 µM. OAL MKN also exhibited higher selectivity toward fungus than mammalian cells. In conclusion, we described the encapsulation of O-allyl-lawsone in 2-hydroxypropyl-ß-cyclodextrin, increasing the antiparasitic activity compared with the free form and reducing the cytotoxicity and increasing the selectivity towardSporothrix yeasts and the T. cruzi trypomastigote form. This study highlights the potential development of this inclusion complex as an antiparasitic and antifungal agent to treat neglected diseases.
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Doença de Chagas , Naftoquinonas , Trypanosoma cruzi , Animais , 2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/uso terapêutico , Antiparasitários/uso terapêutico , Doença de Chagas/tratamento farmacológico , Mamíferos , Naftoquinonas/uso terapêuticoRESUMO
Biomolecular condensates, membrane-less entities arising from liquid-liquid phase separation, hold dichotomous roles in health and disease. Alongside their physiological functions, these condensates can transition to a solid phase, producing amyloid-like structures implicated in degenerative diseases and cancer. This review thoroughly examines the dual nature of biomolecular condensates, spotlighting their role in cancer, particularly concerning the p53 tumor suppressor. Given that over half of the malignant tumors possess mutations in the TP53 gene, this topic carries profound implications for future cancer treatment strategies. Notably, p53 not only misfolds but also forms biomolecular condensates and aggregates analogous to other protein-based amyloids, thus significantly influencing cancer progression through loss-of-function, negative dominance, and gain-of-function pathways. The exact molecular mechanisms underpinning the gain-of-function in mutant p53 remain elusive. However, cofactors like nucleic acids and glycosaminoglycans are known to be critical players in this intersection between diseases. Importantly, we reveal that molecules capable of inhibiting mutant p53 aggregation can curtail tumor proliferation and migration. Hence, targeting phase transitions to solid-like amorphous and amyloid-like states of mutant p53 offers a promising direction for innovative cancer diagnostics and therapeutics.
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Neoplasias , Ácidos Nucleicos , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo , Agregados Proteicos , Neoplasias/metabolismo , Amiloide/químicaRESUMO
Pharmaceutical chemistry has many industrial processes that must be studied and adapted to a new reality where the environment must be the focus of all production chains. Thus, new technologies that are cleaner and use renewable sources of raw materials still need to be developed and applied to materials that go to the market, and they need to reach a level that is less harmful to the environment. This applies especially in areas related to the pharmaceutical industries since chemical products are used in the production of medicines and used in many other areas of everyday life and are included in the Sustainable Development Goals proposed by the United Nations. This article intends to provide insight into some relevant topics that can stimulate researchers toward medicinal chemistry that can contribute to a sustainable future of the biosphere. This article is structured around four interconnected themes that influence how green chemistry can be important for a future where science, technology and innovation are key to mitigating climate change and increasing global sustainability.
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Química Farmacêutica , Desenvolvimento SustentávelRESUMO
With 53 formally described species, the genus Cypretta is one of the most common freshwater ostracod genera in the world. It has a mainly circumtropical distribution. The type species, Cypretta tenuicauda (Vávra, 1895), was described from Zanzibar (Africa) in a superficial way. Therefore, the morphology and identity of this species and of the genus remained problematic until today. Here, we redescribe Cypretta tenuicauda from the original type material and discuss the morphology of the species and the diagnosis of the genus. The species is characterized by the presence of anterior marginal septa in both valves, the sub-triangular carapace shape in lateral view, the right valve overlapping the left valve, the generally wide carapace and the presence of a serrated posteroventral inner list in the right valve. In addition, both α and ß setae on the mandibular palp are long and thin, claws Ga and Gp on the caudal ramus are elongated and seta-like, while the caudal ramus itself is equally slender. The caudal ramus attachment is reduced to a simple branch. The present redescription of the type species will assist in creating order in what is now a taxonomically confused genus.
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Crustáceos , Água Doce , Animais , Distribuição Animal , MandíbulaRESUMO
We describe seven new species in two new genera of the Physocypria sensu latu clade (Cyclocypridinae) from three of the main Brazilian floodplains. Brasilocypria pea gen. et spec. nov. and Brasilocypria ricardopintoi gen. et spec. nov. occur in the Upper Paraná River floodplain and the South Matogrossense Pantanal, Claudecypria mesquitai gen. et spec. nov., Brasilocypria alisonae gen. et spec. nov. and Claudecypria rochei gen. et spec. nov. were found in the South Matogrossense Pantanal, and Brasilocypria lordi gen. et spec. nov. and Brasilocypria namiotkoi gen. et spec. nov. occur in the Amazon River floodplain. All new species here described were found as sexual populations. Generally, they have a short and suboval carapace, with the left valve overlapping the right valve on all sides, except for the dorsal side in some species. The morphology of the hemipenis and the prehensile palps, together with the shape of the valves, were the most important characters to distinguish the species. Size differences between species can be substantial. Several characters, such as the absence in all new species of the short accompanying seta of the five natatory setae on the antenna; the presence in all new species of a long seta next to the two a-setae on the first thoracopod, and the presence/absence or differences in length of specific setae on the second and third thoracopod, are relevant for the generic diagnoses. We also redefine Keysercypria Karanovic, 2011.
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Crustáceos , Rios , Animais , BrasilRESUMO
Beetroot is a tuber rich in antioxidant compounds, i.e., betanin and saponins, and is one of the main sources of dietary nitrate. The aim of the present study was to microencapsulate a ready-to-eat beetroot soup by lyophilization using different encapsulating agents, which supply the required amount of bioactive nutrients. Particle size distributions ranged from 7.94 ± 1.74 to 245.66 ± 2.31 µm for beetroot soup in starch and from 30.56 ± 1.66 to 636.34 ± 2.04 µm in maltodextrin. Microparticle yields of powdered beetroot soup in starch varied from 77.68% to 88.91%, and in maltodextrin from 75.01% to 80.25%. The NO3- and total betalain contents at a 1:2 ratio were 10.46 ± 0.22 mmol·100 g-1 fresh weight basis and 219.7 ± 4.92 mg·g-1 in starch powdered beetroot soup and 8.43 ± 0.09 mmol·100 g-1 fresh weight basis and 223.9 ± 4.21 mg·g-1 in maltodextrin powdered beetroot soup. Six distinct minerals were identified and quantified in beetroot soups, namely Na, K, Mg, Mn, Zn and P. Beetroot soup microencapsulated in starch or maltodextrin complied with microbiological quality guidelines for consumption, with good acceptance and purchase intention throughout 90 days of storage. Microencapsulated beetroot soup may, thus, comprise a novel attractive strategy to offer high contents of bioaccessible dietary nitrate and antioxidant compounds that may aid in the improvement of vascular-protective effects.
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Biopolymers obtained from natural macromolecules are noteworthy among materials presenting high biocompatibility and adequate biodegradability, as is the case of chitosan (CS), making this biopolymeric compound a suitable drug delivery system. Herein, chemically-modified CS were synthetized using 2,3-dichloro-1,4-naphthoquinone (1,4-NQ) and the sodium salt of 1,2-naphthoquinone-4-sulfonic acid (1,2-NQ), producing 1,4-NQ-CS and 1,2-NQ-CS by three different methods, employing an ethanol and water mixture (EtOH:H2O), EtOH:H2O plus triethylamine and dimethylformamide. The highest substitution degree (SD) of 0.12 was achieved using water/ethanol and triethylamine as the base for 1,4-NQ-CS and 0.54 for 1,2-NQ-CS. All synthesized products were characterized by FTIR, elemental analysis, SEM, TGA, DSC, Raman, and solid-state NMR, confirming the CS modification with 1,4-NQ and 1,2-NQ. Chitosan grafting to 1,4-NQ displayed superior antimicrobial activities against Staphylococcus aureus and Staphylococcus epidermidis associated with improved cytotoxicity and efficacy, indicated by high therapeutic indices, ensuring safe application to human tissue. Although 1,4-NQ-CS inhibited the growth of human mammary adenocarcinoma cells (MDA-MB-231), it is accompanied by cytotoxicity and should be considered with caution. The findings reported herein emphasize that 1,4-NQ-grafted CS may be useful in protecting injured tissue against bacteria, commonly found in skin infections, until complete tissue recovery.
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Epoxy-α-lapachone (ELAP), an oxirane-functionalized molecule synthesized from naturally occurring lapachol, has shown promising activity against murine infection with Leishmania (Leishmania) amazonensis. Herein, we report the successful development of oil-in-water-type (o/w) microemulsions (ME) loaded with ELAP (ELAP-ME) using Capmul MCM, Labrasol, and PEG 400. Stability studies revealed that ELAP-ME (100 µg/mL of ELAP), which was comprised of globule size smaller than 120.4 ± 7.7 nm, displayed a good stability profile over 73 days. ELAP-ME had an effect in BALB/c mice infected with L. (L.) amazonensis, causing reductions in paw lesions after two weeks of treatment (â¼2-fold) when compared to untreated animals. Furthermore, there was also a reduction in the parasite load both in the footpad (60.3%) and in the lymph nodes (31.5%). Based on these findings, ELAP-ME emerges as a promising treatment for tegumentar leishmaniasis.