Amphotericin B (AmB) is a very potent antifungal drug with very rare resistance among clinical isolates. Treatment with the AmB formulations available currently is associated with severe side effects. A promising strategy to minimize the toxicity of AmB is reducing its dose by combination therapy with other antifungals, showing synergistic interactions. Therefore, substances that display synergistic interactions with AmB are still being searched for. Screening tests carried out on several dozen of synthetic 1,3,4-thiadiazole derivatives allowed selection of a compound called 4-(5-methyl-1,3,4-thiadiazole-2-yl) benzene-1,3-diol (abbreviated as C1), which shows strong synergistic interaction with AmB and low toxicity towards human cells. The aim of the present study was to investigate the type of in vitro antifungal interactions of the C1 compound with AmB against fungal clinical isolates differing in susceptibility. The results presented in the present paper indicate that the C1 derivative shows strong synergistic interaction with AmB, which allows the use of a dozen to several dozen times lower AmB concentration necessary for 100% inhibition of the growth of pathogenic fungi in vitro. Synergistic interactions were noted for all tested strains, including strains with reduced sensitivity to AmB and azole-resistant isolates. These observations give hope for the possibility of application of the AmB - C1 combinatory therapy in the treatment of fungal infections.
Compounds belonging to the group of 5-substituted 4-(1,3,4-thiadiazol-2-yl) benzene-1,3-diols exhibit a broad spectrum of biological activity, including antibacterial, antifungal, and anticancer properties. The mechanism of the antifungal activity of compounds from this group has not been described to date. Among the large group of 5-substituted 4-(1,3,4-thiadiazol-2-yl) benzene-1,3-diol derivatives, the compound 4-(5-methyl-1,3,4-thiadiazole-2-yl) benzene-1,3-diol, abbreviated as C1, was revealed to be one of the most active agents against pathogenic fungi, simultaneously with the lowest toxicity to human cells. The C1 compound is a potent antifungal agent against different Candida species, including isolates resistant to azoles, and molds, with MIC100 values ranging from 8 to 96 μg/ml. The antifungal activity of the C1 compound involves disruption of the cell wall biogenesis, as evidenced by the inability of cells treated with C1 to maintain their characteristic cell shape, increase in size, form giant cells and flocculate. C1-treated cells were also unable to withstand internal turgor pressure causing protoplast material to leak out, exhibited reduced osmotic resistance and formed buds that were not covered with chitin. Disturbances in the chitin septum in the neck region of budding cells was observed, as well as an uneven distribution of chitin and β(1→3) glucan, and increased sensitivity to substances interacting with wall polymerization. The ATR-FTIR spectral shifts in cell walls extracted from C. albicans cells treated with the C1 compound suggested weakened interactions between the molecules of β(1→3) glucans and β(1→6) glucans, which may be the cause of impaired cell wall integrity. Significant spectral changes in the C1-treated cells were also observed in bands characteristic for chitin. The C1 compound did not affect the ergosterol content in Candida cells. Given the low cytotoxicity of the C1 compound to normal human dermal fibroblasts (NHDF), it is possible to use this compound as a therapeutic agent in the treatment of surface and gastrointestinal tract mycoses.
In modern pharmacology, compounds of natural origin are gaining more and more recognition. One of them is warfarin, which is a compound of organic coumarin derivatives. It is used medicinally in the anticoagulant doctor. This compound was commercially introduced to the United States in the 1950s. It has been available on the Polish market since 2006. Warfarin is an antagonist of vitamin K. It works by inhibiting the synthesis of vitamin K in the liver and thus blocking the synthesis of vitamin K dependent blood clotting factors (II, VII, IX, X). It is widely used by people suffering from cardiovascular diseases such as venous thrombosis and venous embolism. Adopted by patients with suspected or after a heart attack. Despite its undisputed positive effect, one should remember about the numerous side effects resulting from long-term use of warfarin. They may be due to intolerance to this compound, which causes nausea, vomiting, and allergic reactions. Moreover, recent studies show that it may have a destructive effect on the liver and cause calcification of blood vessels. Keep in mind that warfarin can interact with many substances you are taking for other medical conditions. Agents that increase the effects of warfarin include antibiotics such as erythromycin, deoxicillin, commonly used drugs containing caffeine, acetylsalicylic acid and naturally derived compounds found in ginkgo, garlic and sage. Compounds that weaken the effect of warfarin are barbiturates, cyclosporine, vitamin C, and St. John's wort.
Carotenoids are compounds of natural origin and are a product of secondary metabolism of plants and bacteria. These are chemically unsaturated hydrocarbons that act as dyes with a wide range of colors. These compounds are stored in chloroplasts and chromatophores. In living organisms, they are used in the photosynthesis process, have a protective function in the photooxidation process and are designed to neutralize free radicals. Due to the difference in structure, the molecules were divided into 2 groups, i.e. orange-carotenes and yellowxanthophylls. Due to their unique antioxidant properties, they are widely used in the cosmetics industry. Carotenoids as antioxidants have a beneficial effect on human health and well-being. Currently, the most popular compounds that are used in cosmetology are carotene and lycopene. The development of cosmetology followed the development of biochemistry, chemistry, pharmacy and medicine. Compounds used in care products can be obtained as extracts from plants or obtained by chemical synthesis or biotechnological processes. It can be seen that in recent years the awareness of the use of cosmetic products has increased. This contributed to the increased interest in cosmetics of natural origin. Thanks to the interest in natural / ecological products, we have the opportunity to get to know biologically active substances better and to fully use them in cosmetology, pharmacology and medicine
Introduction. Alkaloids are a large group of organic compounds of natural origin. One of the most popular alkaloids is magnoflorine. This compound is synthesized by plants from the Ranunculaceae, Menispermaceae and Magnoliaceae families. Magnoflorine has unique biological properties and a broad spectrum of physiotherapeutic activity. It has antibacterial, antifungal, antidiabetic, immunomodulating and anticancer properties. Objective.The aim of the study is to present magnoflorine as a compound with anti-cancer potential. Brief description of the state of knowledge. Magnoflorine is a compound belonging to the isoquinolone alkaloids. Metabolized by secondary metabolism it is most commonly collected in the roots, rhizomes, tubers and bark of plants. It can be isolated from all plant elements by chromatographic methods. Magnoflorine has a number of therapeutic properties, including anti-cancer. Magnoflorine has been shown to inhibit cell proliferation, migration and cause apoptosis. The possibility of using this compound in the treatment of breast and stomach cancer has been confirmed. Results. The combination of DOX with magnoflorine reduces the expression of Bcl-2 and enhances the cleavage of caspase-9 and-3, causing apoptosis in breast cancer cells. Moreover, they block the activation of PI3K / AKT / mTOR signaling, which play an important role in regulating tumour growth. Magnoflorine inhibits the activity of caspases in liver cancer cells, resulting in inhibition of proliferation. Conclusion. Magnoflorine is an interesting research target due to its unique anticancer properties. Detailed knowledge of the pharmacological possibilities of magnoflorine will enable its effective use in the prevention and treatment of many civilization diseases.
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