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New 1,2,4-triazole potential inhibitors of mycobacterial imidazoleglycerol-phosphate dehydratase (IGPD)

Mycobacterium tuberculosis, especially its multi-resistant strains, poses a serious threat to human health, and therefore, the development of new anti-tuberculosis agents is an important trend in new biologically active compounds search. 1,2,4-Triazole is a privileged fragment of antibacterial drugs, including anti-tuberculosis agents. A number of macromolecular targets are known for M. tuberculosis, among which special attention deserves imidazoleglycerol-phosphate dehydratase (IGPD) – the enzyme catalyzing the sixth reaction of histidine bacterial biosynthesis. This enzyme can be considered a selective target of anti-tuberculosis therapy due to the lack of human orthologs. Some researchers previously shown that some of compounds with 1,2,4-triazole fragments inhibits IGPD. According to those authors, 1,2,4-triazole is able to mimic the heterocycle of IGPD substrate – imidazole glycerol phosphate. In the proposed work, a number of high model affinity to the IGPD catalytic site new derivatives of 5-aminomethyl-1,2,4-triazole-3-carboxamides were synthesized. The antimicrobial potential of these compounds was tested against the M. smegmatis. Non-pathogenic M. smegmatis were used as a model of M. tuberculosis due to the high conservativeness of IGPD and similarities in cell wall structure and metabolism in the genus Mycobacterium. According to the primary results a number of 5-aminomethyl-1,2,4-triazole-3-carboxamide derivatives show the inhibition of the M. smegmatis microbial growth. Moreover, experimental data showed that the greatest activity was shown by those compounds whose affinity for the model of the catalytic center of the enzyme was higher. This suggests that the new compounds may be active by binding to the catalytic site of IGPD.

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Study of lectin like protein from Terminalia catappa (TC) seeds for its physicochemical and antimicrobial properties
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Lectins are a diverse group of proteins crucial in numerous biological activities. They exist in plants, animals, and microorganisms, each with unique structural and functional characteristics. Their ability to exhibit hemagglutination and specifically bind with carbohydrates allows lectins to participate in processes like cell adhesion, immune responses, and intracellular signaling pathways. Lectins are particularly noted for their roles in counteracting viral diseases, regulating blood sugar levels, and fending off pathogens, and preventing cancer progression. These natural compounds offer potential therapeutic benefits in various healthcare applications. Terminalia catappa (TC), known as Indian almond, is a large tropical tree containing flavonoids, tannins, saponins, and phytosterols with medicinal values. This research aimed to investigate the partial purification and characterization of lectins from TC seeds. The process involved extracting and partially purifying the lectin, testing it for hemagglutination assay, temperature and pH stability, EDTA dependence, effect of metal ions, specific sugar determination, and antibacterial activity. Hemagglutination activity was observed in human blood group B+. The findings suggest TC seed lectin is remarkably stable within a moderate temperature range and across a broad pH spectrum. The dependence on EDTA for hemagglutination activity indicates a potential metalloprotein nature, with notable interactions with various metal ions, except Hg²⁺. While the initial antimicrobial assessment against common bacteria yielded limited results, further studies hold promise for uncovering the full potential of TC seed lectin in healthcare and therapeutic advancements.

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QUEEN BEE ACID 10H2DA HALTS HCT-116 CELLS’ COLLECTIVE MIGRATION VIA ELEVATION OF E-CADHERIN AND β-CATENIN

Particular interest in oncology presents motility of cancer cells and the existence of two main types of migration, collective and individual largely dependent on parameters of intercellular connections, E-cadherin and β-catenin. However, the switch between these two types of migration greatly complicates this disease and add further complexity to therapeutic approaches. A unique and specific component of bee product royal jelly is 10HDA unsaturated fatty acid, with unknown effects on migration of colorectal carcinoma cells and the exact molecular mechanism so far.

Therefore, this study assessed the collective migratory capacity of HCT-116 colorectal carcinoma cells by using Wound healing method, 24 h after treatment with 10H2DA in two selected concentrations (10 and 100 μM). Additionally, the protein expression of E-cadherin and β-catenin was monitored by applying immunofluorescent assay.

Our study highlights the prominent dose-dependent antimigratory effects of 10H2DA on HCT-116 cells, which is obviously due to the significant inhibition of two tested membrane markers, E-cadherin and β-catenin. The suppression of these two components of intercellular junction complexes and HCT-116 cells’ motility is obviously in tight association, implying their importance in CRC cells aggressiveness.

Overall, 10H2DA is valuable source of anticancer potential worth of further investigation on CRC, especially regarding cell motility in association with aforementioned adhesion molecules.

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ABSORPTION OF FREE RADICALS OF NEW S-DERIVATIVES (1,2,4-TRIAZOLE-3(2H)-YL)METHYL)THIOPYRIMIDINES

Pyrimidine-2-thiols are widely used in medicinal chemistry due to a wide range of biological activity. They are precursors of important organic compounds and organometallic complexes. At the current stage of the development of organic chemistry, many basic synthetic approaches to the synthesis of 1,2,4-triazole, which exhibits high antibacterial and fungicidal activity, have been developed. The relevance of the study of 1,2,4-triazole derivatives with a pyrimidine fragment is due to the synthesis of potential antibacterial drugs with a wide spectrum of action, the search for molecular descriptors of their structure, which are important for establishing the laws of "structure - biological activity". The obtained synthetic hybrids can be promising in the search for biologically active substances with antineoplastic, antibacterial, analgesic, antidiabetic activity, antihypertensive agents and other types of biological action among this range of compounds. Absorbance was measured at 516 nm. The control was a solution of 2.00 ml of 0.1 mM DPPH solution in the presence of 2.00 ml of methanol, the standard was ascorbic acid. It is worth noting that the compound has a value of antioxidant activity = 83.86%, which exceeds the activity of the comparison drug - the natural antioxidant ascorbic acid. High activity may be associated with the presence of pharmacophore fragments - a natural absorber of pyrimidine free radicals and a Sulfur atom connected to 1,2,4 triazole.

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Evaluation of the photostability of Ivermectin
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Ivermectin (IVM) is a pharmaceutical antiparasitic agent with a broad range of medicinal properties that are comparable in impact to those of penicillin and aspirin. The molecule's structural composition includes functional groups that indicate the potential for photoreactivity. However, there is a paucity of information regarding its photostability, particularly in tropical regions where parasitic diseases and intense solar radiation intersect. It would be beneficial to investigate the chemical transformation of this compound in a variety of natural aqueous environments under different irradiation sources. This knowledge gap motivated this study. Therefore, the chemical alterations of IVM were investigated in various natural aqueous media when exposed to solar radiation (UVA-Vis). In particular, an evaluation of its photostability was conducted at wavelengths of 350 and 254.5 nm. It is noteworthy that photodegradation occurred primarily at 350 nm. Additionally, IVM demonstrated photohemolytic effects on human erythrocytes, indicating phototoxicity. This suggests the presence of photoinduced mechanisms by this drug for the generation of free radicals, including singlet oxygen (1O2, type II mechanism), superoxide anion, and hydroxyl radical (.O2 and .OH, type I mechanism). The latter would also entail the interaction of the IVM molecule with the membrane of human red blood cells, which would signify a considerable biological impact. Furthermore, through computational calculations, potential photoproducts formed during IVM irradiation were deduced, simulating experimental conditions. Our findings contribute to an enhanced comprehension of IVM's behavior under solar exposure, particularly in tropical contexts. Additional research is imperative to address its emerging biological activity status and potential implications for biomedical applications

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Olive residues as a source of bioactive compounds

The production of olive oils implies the generation of high quantities of solid residues and/or wastewaters that may have a great impact on terrestrial and aquatic environments because of their phytotoxicity. Alperujo is a combination of liquid and solid waste of olive oil processing, few studies are known that show their high biological potential. Indeed, wastes remaining after the production of olive oil are a heterogeneous mixture of many chemical components, such as metal ions, carbohydrates, and polyphenols that may exert different biological activities, primarily acting as antioxidant.

The samples of “alperujo” were obtained as waste given from industries that work on olive oil production. Three ethanolic organic extracts were prepared using solvent maceration, ultrasound and reflux extraction methods. Yields of each extract were determined and evaluated for their ability to trap free radicals, using the DPPH and ABTS assays contributing to the calculation of SC50 (free radical scavenging). The extracts were subjected to preliminary phytochemical testing, analyzing phenolic content by Folin method and heavy metals concentration using atomic absorption spectrometry. The extraction method was decisive for the yield obtained, with the reflux system being highly efficient, the antioxidant activity show the potential of these wastes as a source of bioactive compounds of interest for possible reuse.

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ISOLATION, CHARACTERIZATION AND STRUCTURAL ELUCIDATION OF TWO COUMARIN COMPOUNDS FROM THE CHLOROFORM FRACTION OF SCADOXUS MULTIFLORUS (MARTYN) RAF. (AMARYLLIDACEAE)
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Scadoxus multiflorus belonging to the family Amaryllidaceae, is a flowering plant, first introduced by Thomas Martyn in 1795 as Haemanthus multiflorus. In 1838, Constantine Samuel Rafinesque changed the genus of H. multiflorus by a new genus Scadoxus. The flower is also known as fire-ball lily, African blood lily, powderpuff lily, pincushion flower, and so on. Scadoxus multiflorus, is a fleshy herbaceous plant with a large bulb bearing leaves of 25 cm long and 8 cm wide which appear during the rainy season. It is used in ethno-medicine in the management of malarial, the ointment is use for treating ulcers, as stimulant in debility and cardio tonic activity. In the present work, the aerial parts of Scadoxus multiflorus was extracted with methanol using maceration process, the crude methanol extract was partitioned with hexane, chloroform, ethyl acetate and butanol. Extensive phytochemical separation of chloroform fraction of MAE followed by isocratic elusion lead the isolation of two coumarin compounds identified as 2-methyl-2H-chromen-7-ol and 7-methoxy-2H-chromen-2-one. The two isolated compounds were subjected to physicochemical analysis (chemical test, melting point determination and solubility test). And the structure of the compounds were elucidated using UV, FT- IR, and 1D, 2D NMR spectroscopy and the structure was name using ChemDraw.

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The Effect of pH on the Hydrolysis of Acetylsalicylic Acid (C9H8O4) to Salicylic Acid (C7H6O3) and Acetic Acid (C2H4O2) at 333.15 K (60°C): A Spectrophotometric Analysis

This study investigates the effect of pH on the hydrolysis of acetylsalicylic acid (C9H8O4) to salicylic acid (C7H6O3) and acetic acid (C2H4O2) at a temperature of 333.15 K (60°C). The hydrolysis reaction was systematically analyzed by measuring the concentration of salicylic acid using spectrophotometry across a range of pH levels (2.0, 4.0, 6.0, 8.0, and 10.0). The results reveal a clear trend: as the pH increases, the concentration of salicylic acid also increases. This observation indicates that acetylsalicylic acid exhibits reduced stability in more basic conditions, leading to a higher rate of hydrolysis in alkaline environments.

The findings support the hypothesis that the hydrolysis rate of acetylsalicylic acid is indeed pH-dependent, with higher pH levels significantly accelerating the reaction. This conclusion is consistent with previous research and enhances our understanding of the chemical behavior of aspirin under varying pH conditions. Specifically, the data suggest that the stability of acetylsalicylic acid decreases as the environment becomes more alkaline, resulting in increased formation of salicylic acid.

These results have important implications for pharmaceutical sciences and medicine. The pH-dependent hydrolysis of acetylsalicylic acid highlights the necessity of considering the pH of the gastrointestinal tract when evaluating the stability and absorption of aspirin. In the acidic environment of the stomach, aspirin remains relatively stable, while in the more basic conditions of the small intestine, it is more prone to hydrolysis. This understanding is crucial for optimizing the therapeutic efficacy of aspirin and minimizing potential gastrointestinal side effects.

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Formulation of Alginate and Pectin-Based Beads Encapsulating Trichoderma for Sustainable and Efficient Agriculture
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The formulation of polysaccharides-based beads encapsulating Trichoderma spp. represents an eco-friendly strategy for promoting sustainable and efficient agriculture [1]. Trichoderma, a beneficial fungus, is well-known for its ability to enhance plant growth, combat phytopathogens, and improve soil health [2]. Encapsulating Trichoderma spores in a polysaccharide matrix provides a protective environment that ensures their viability and facilitates their controlled release into the soil.

Alginate is a natural anionic polymer found in various species of brown algae and certain bacteria. Pectin is an heteropolysaccharide present naturally in the cell walls of all higher plants. Due to their distinctive characteristics [3,4], alginate and pectin are regarded as promising carrier materials for the encapsulation of bioactive agents.

In this work, alginate (Alg) beads, pectin (Pec) beads extracted from orange peel, and Alg/Pec composite beads in a 50/50 (w/w) ratio encapsulating Trichoderma S1 (1.83. 104 conidia/mL ) and S2 (1.56.108 conidia/mL ) were prepared using the ionic gelation method. The Moisture content of the prepared beads was evaluated. The size and shape of the beads were determined by analyzing images obtained by an optical microscope XE3910. The average size of the microcapsules (wet) varied from 1886 ± 6.557 μm to 1942 ± 28.688 μm . All samples were characterized by Fourier transform infrared spectroscopy (FTIR). The overall results demonstrated the successful encapsulation of Trichoderma spp. and highlighted the effects of the different formulations on the physicochemical properties of the beads.

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Highly efficient hydrolysis of Hesperidin, Naringin and synthesis of their aglycone acetates under microwave irradiation.

Hesperidin and naringin are glycosides present in the peels of rutaceae fruits (orange (Citrus sinensis ) for hesperidin ), grapefruit (Citrus paradise) for naringin) and are easily extracted with ethanol. Acidic hydrolysis of Hesperidin and Naringin, furnishing their aglycone moieties Hesperetin and Naringenin respectively, is reported using sulfuric acid and water as solvent, under microwave irradiation. This new economical procedure provides the flavanones in very good yields ~90%, better than of acid hydrolysis in reflux.

Hesperetin is a flavanone that exhibits analgesic, antinociceptive, anti-inflammatory, antioxidative, cardioprotective properties. Naringin is a flavonoid compound, which can be used to treat or prevent various diseases, such as obesity, heart disease, diabetes, and metabolic syndrome. The medicinal value of naringin is mainly reflected in its antioxidant and anti-inflammatory functions, and it has a protective effect on pathophysiology.

Furthermore, we describe for the first time, an efficient synthesis of Hesperidin- octaacetate, Naringin-octaacetate, Hesperetin-triacetate and Naringenin-triacetate from the corresponding flavanones, in the presence of 4-(N,N-dimethylamino)- pyridine DMAP as catalyst, under microwave irradiation.

Hesperidin, Naringin, Hesperetin and Naringenin are water soluble and theirs acetates are liposoluble. The formation of polyacetate makes it possible to increase the liposolubility of flavones and their aglycones while being prodrugs because they are easily hydrolyzable into flavones and aglycones in living beings.

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