Theranostics combines therapeutic and imaging diagnostic techniques that are extremely dependent on the action of imaging agent, transporter of therapeutic molecules, and specific target ligand, in ...which fluorescent probes can act as diagnostic agents. In particular, naphthoimidazoles are potential bioactive heterocycle compounds to be used in several biomedical applications. With this aim, a group of seven naphth1,2-
imidazole compounds were synthesized from β-lapachone. Their optical properties and their cytotoxic activity against cancer cells and their compounds were evaluated and confirmed promising values for molar absorptivity coefficients (on the order of 10
to 10
), intense fluorescence emissions in the blue region, and large Stokes shifts (20-103 nm). Furthermore, the probes were also selective for analyzed cancer cells (leukemic cells (HL-60). The naphth1,2-
imidazoles showed IC
between 8.71 and 29.92 μM against HL-60 cells. For HCT-116 cells, values for IC
between 21.12 and 62.11 μM were observed. The selective cytotoxicity towards cancer cells and the fluorescence of the synthesized naphth1,2-
imidazoles are promising responses that make possible the application of these components in antitumor theranostic systems.
Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search ...for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with general structure R1R2C = NNR3R4, were synthesized with molecular modification strategies. In this paper, we describe the ability of hydrazone derivatives to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In both experimental models, the hydrazone with the greatest potency (H5) significantly (p < 0.05) reduced nociceptive behavior. Additionally, methods of acute and chronic inflammation induced by different chemicals (carrageenan and histamine) were performed to evaluate the anti-inflammatory effect of H5. Moreover, molecular docking analysis revealed that H5 can block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. H5 also changes locomotor activity. In summary, H5 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.
Antimicrobial resistance in bacteria, such as
Staphylococcus aureus
, has been the subject of many assistance studies of alternatives for the treatment of infections. These studies aim to solve this ...problem for bacteria, such as biofilm formation. Aiming to control the emergence of the problem or enhance antibiotic activity, the data sources are inserted into new therapeutic alternatives for the treatment of infections. β-Lapachone and Lapachol Oxime are semi-synthetic derivatives of Lapachol with antimicrobial potential. Clinical isolates from human blood cultures were used in this study. Scanning electron microscopy (SEM) was performed following the glutaraldehyde fixation protocol. The presence of β-Lapachone and Lapachol Oxima interfered in the biofilm formation state. In the MEV, the effect was observed in the reduction of the population of biofilm-forming cells. Therefore, it was possible to conclude the promising potential of the anti-biofilm of substances, justifying the nature of the natural products as agents of inspiration for the detection of new compounds with the biological function.
Systematic review of the last decade’s thiosemicarbazones leishmanicidal potential.
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Thiosemicarbazones constitute a class of organic compounds with the general structure R=N-NH-CS-NHR ...and are known for their biological properties, making them an important structure for drug development. This work presents a systematic review of the main publications from the last decade (2013–2023) reporting the leishmanicidal potential of thiosemicarbazones. A search was conducted in three databases: Web of Science, Science Direct, and SciFinder, using the following singular English descriptors, ‘thiosemicarbazone’ and ‘leishmanicidal.’ During the selection process, 25 articles were identified, 12 were excluded due to duplication, and 5 were excluded for not meeting the pre-defined inclusion criteria. As a result, 8 articles were selected for discussion in this systematic review. In the reviewed studies, 118 thiosemicarbazones were synthesized and tested in vitro for their activity against protozoa of the Leishmania genus. In three of these studies, researchers identified thiosemicarbazones with promising results and chose to go deeper into their investigation. Given the significant leishmanicidal activity observed in thiosemicarbazones studied over the past 10 years, coupled with the scarcity of publications – less than one article per year – it is evident that this represents a promising research field.
Bioprospecting and synthesis of strategically designed molecules have been used in the search for drugs that can be in leishmaniasis. Hydrazones (HDZ) are promising compounds with extensive ...biological activities. The objective of this work was to perform in silico studies of hydrazones 1–5 and to evaluate their antileishmanial, cytotoxic and macrophage immunomodulatory potential in vitro. Hydrazones were subjected to prediction and molecular docking studies. Antileishmanial protocols on promastigotes and amastigotes of Leishmania amazonensis, cytotoxicity and macrophage immunomodulatory activity were performed. Hydrazones showed a good pharmacokinetic profile and hydrazone 3 and hydrazone 5 were classified as non-carcinogenic. Hydrazone 5 obtained the best conformation with trypanothione reductase. Hydrazone 1 and hydrazone 3 obtained the best mean inhibitory concentration (IC50) values for promastigotes, 4.4–61.96 μM and 8.0–58.75 μM, respectively. It also showed good activity on intramacrophagic amastigotes, with hydrazone 1 being the most active (IC50 = 6.79 μM) with selectivity index of 56. In cytotoxicity to macrophages hydrazone 3 was the most cytotoxic (CC50 = 256.3 ± 0,04 μM), while hydrazone 4 the least (CC50 = 1055.9 ± 0.03 μM). It can be concluded that the hydrazones revealed important pharmacokinetic and toxicological properties, in addition to antileishmania potential in reducing infection and infectivity in parasitized macrophages.
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•HDZs showed good pharmacokinetic and toxicological profile;•HDZ-5 showed better action on TryR;•The hydrazones (HDZ) showed potent antileishmanial activity in vitro for promastigotes and amastigotes;•HDZ-1 obtained the best selectivity index (SI), higher than Amphotericin B;•HDZ were able to induce activation of macrophages.
SEMICARBAZONES: INTERDISCIPLINARY APPROACH IN EXPERIMENTAL CLASSES OF ORGANIC CHEMISTRY AND MEDICINAL CHEMISTRY. Considering the chemical and pharmacological properties of semicarbazones, an ...interdisciplinary didactic sequence was developed to be applied in experimental classes of undergraduate courses in Pharmacy, Chemistry and related areas. This didactic sequence was planned in three steps, starting from the planning of the target molecule, a semicarbazone derived from helional, to its synthesis, physicochemical characterization (CCD, melting point, FTIR and UV-Vis) and in silico tests of its pharmacokinetic properties using the free software ADMETlab 2.0. The proposed target molecule has as molecular scaffold the 1,3-benzodiaxole nucleus and the semicarbazone function, aiming to obtain a molecule with promising anticonvulsant action and that can be obtained by a low cost and easy to execute methodology, which makes it attractive for use in experimental classes. Thus, the application of this didactic sequence aims to provide undergraduate students the opportunity to experience the process of drug development, applying techniques for planning, synthesis, characterization, and pharmacokinetic evaluation in silico. Besides reinforcing the interdisciplinary teaching of Medicinal Chemistry, applying in an integrated way the theoretical and practical knowledge of the disciplines of Organic Chemistry, Physical Chemistry, Pharmacology and Computational Chemistry.
Resumo O presente estudo refere-se ao impacto do uso de agrotóxicos sobre a saúde humana no Submédio do Vale do São Francisco. Por meio de entrevistas objetivou-se analisar a influência dos ...condicionantes sociais, culturais e econômicos no processo saúde-doença dos trabalhadores expostos a agrotóxicos. Para a coleta de dados foram entrevistados 339 trabalhadores rurais de perímetros irrigados dos municípios de Juazeiro-BA e Petrolina-PE. Todos do sexo masculino, sendo 182 (53,7%) proprietários rurais e 157 (46,3%) empregados, predominando indivíduos entre 40 e 59 anos entre os proprietários e abaixo de 39 anos entre os trabalhadores. Mais de 50% apresentou baixo nível de escolaridade e 55,2% tinha rendimentos mensais menor ou igual a 2 salários mínimos. Muitos sabem da importância do uso de EPIs e da obrigatoriedade do receituário agronômico para a utilização e a compra de agrotóxicos, entretanto cerca de 40% não usam EPIs ou fazem uso de forma incompleta e 28,9% não apresentam receituário durante a compra. Mais de 9% dos participantes relataram casos de intoxicação, no entanto, menos de 7% procuraram atendimento especializado. Os trabalhadores sabem que o uso de agrotóxicos nas lavouras os expõem a situações de risco, mas essa informação não é suficiente para alterar a conduta no exercício laboral.
Abstract This study refers to the impact of the use of pesticides on human health in the São Francisco River Valley region, in which, through semi-structured interviews, the objective was to analyze the influence of social, cultural and economic determinants on the health-disease process of workers exposed to agrochemicals. For data collection, 339 rural workers from irrigated perimeters of the cities of Juazeiro, in the State of Bahia, and Petrolina, in the State of Pernambuco, were interviewed. All were male, of which 182 (53,7%) were rural owners and 157 (46,3%) were employees, predominantly between 40 and 59 years of age among owners and under 39 among workers. Over 50% have a low level of schooling and 55.2% of them have monthly incomes less than or equal to 2 minimum wages. Many of them know about the importance of wearing personal protective equipment (PPE) and the mandatory license for the use and purchase of agrochemicals. However, about 40% do not use PPE or use it inadequately and 28.9% do not have a license to purchase. More than 9% of participants reported cases of intoxication, however, less than 7% sought specialized care. Workers are aware of the risks that the use of agrochemicals expose them to risk situations, but this does not encourage them to change their worksite behavior.
![Naphth[1,2- d ]imidazoles B...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1420-3049_1433-1373/small "Naphth[1,2- d ]imidazoles Bioactive from β-Lapachone: Fluorescent Probes and Cytotoxic Agents to Cancer Cells")
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