Macronutrients
Chuong Pham-Huy, Bruno Pham Huy in Food and Lifestyle in Health and Disease, 2022
Like cholesterol and phytosterols, mycosterols are sterols present in fungi (mushrooms) (132–133). Ergosterol (24R-methyl-cholesta-5,7,22(E)-trienol) is the main mycosterol found in cell membranes of fungi, yeasts, and protozoa. Ergosterol is a sterol which was first discovered in 1889, in the plant pathogenic ergot fungus Claviceps purpurea (132–133). It is an analog of cholesterol present in mammalian cell membranes. Ergosterol is the major sterol among several sterols present in fungi. Like cholesterol, ergosterol and other mycosterols play similar roles in the permeability and fluidity of fungal cell membranes. They are also needed for fungal growth, a fact that has been exploited in the development of antifungal pesticides widely used in agriculture and antimycotics used to control fungal diseases of humans and animals (132). Ergosterol is converted into vitamin D2 when it is irradiated by sunlight or UV-B. Therefore, cultivated white mushrooms are often exposed to sunlight or UV-B light before marketing to obtain high vitamin D2 levels. Ergosterol also has antioxidant properties (133).
Spices as Eco-friendly Microbicides: From Kitchen to Clinic
Mahendra Rai, Chistiane M. Feitosa in Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
The fungal cell wall is a dynamic structure that protects fungal protoplasts from external osmotic shocks and defines fungal morphogenesis. Thus, changes in the organization or functional disruption of the cell wall induced by antifungal agents are involved in fungal death. The fungal cell membrane is a dynamic structure composed of a lipid bilayer where enzymes and transport proteins are embedded. Ergosterol is a unique sterol found only in the cell membrane of fungi, important for their proper growth and functioning and also acts as an important regulator of membrane fluidity. Thymol have been shown to decrease ergosterol in cell membranes of Candida and Cryptococcus, thereby causing disruption of membrane integrity, membrane-associated enzyme disturbances, extensive damage and, finally cell death (Kowalczyk et al. 2020). Similarly eugenol exerts its antifungal activity on the cell wall and cell membrane of Trichophyton rubrum by disrupting ergosterol biosynthesis and such a result may serve as a guide for future in vivo studies of clinical use of eugenol in treating dermatophyte infections (de Oliveira Pereira et al. 2013).
Monographs of Topical Drugs that Have Caused Contact Allergy/Allergic Contact Dermatitis
Anton C. de Groot in Monographs in Contact Allergy, 2021
Miconazole is a synthetic phenethyl imidazole antifungal agent that can be used topically and by intravenous infusion. This agent selectively affects the integrity of fungal cell membranes, high in ergosterol content and different in composition from mammalian cell membranes. Miconazole is indicated for topical application in the treatment of tinea pedis, tinea cruris, and tinea corporis caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum, in the treatment of cutaneous candidiasis and in the treatment of pityriasis (tinea) versicolor. In pharmaceutical products, miconazole is nearly always employed as miconazole nitrate (CAS number 22832-87-7, EC number 245-256-6, molecular formula C18H15Cl4N3O4); buccal tablets may contain miconazole base (1).
Tailoring and optimization of a honey-based nanoemulgel loaded with an itraconazole–thyme oil nanoemulsion for oral candidiasis
Published in Drug Delivery, 2023
Amal M. Sindi, Waleed Y. Rizg, Muhammad Khalid Khan, Hala M. Alkhalidi, Waleed S. Alharbi, Fahad Y. Sabei, Eman Alfayez, Hanaa Alkharobi, Mohammed Korayem, Mohammed Majrashi, Majed Alharbi, Mohammed Alissa, Awaji Y. Safhi, Abdulmajeed M. Jali, Khaled M. Hosny
As might be seen from the above graphs, ThO has a great capacity for expanding the growth inhibition zones of C. albicans. Ergosterol is a special sterol that can only exist in the outer membrane of a fungus and is crucial to its healthy development and operation. As a result, substances affecting the level of ergosterol might have antifungal properties (Kowalczyk et al., 2020). Thymol, the major component of ThO, has potential antifungal action that is based on how it affects the metabolism of fatty acids, especially ergosterol, in fungal cells (De Lira Mota et al., 2012). Among other things, it produces oxidative stress and an increase in reactive oxygen species, and this lowers the levels of capsular polysaccharide and the extracellular polymer matrix (EPS) (Al-Shahrani et al., 2017). In cell membranes of Candida and Cryptococcus that had been exposed to thymol, ergosterol levels decreased, as previously stated in the literature. This resulted in disruptions of the membrane integrity and membrane-associated enzymes, significant damage, and, ultimately, cell death (Poonam et al., 2019).
Application of the Mannich reaction in the structural modification of natural products
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Miao-Xia Pu, Hong-Yan Guo, Zhe-Shan Quan, Xiaoting Li, Qing-Kun Shen
Compared with the positive control drug ketoconazole (MIC = 62.5 µg·L−1), compound 57 (MIC = 20 µg·L−1) had a higher inhibitory effect on the growth of C. albicans. Moreover, C. glabrata ATCC 2001 showed sensitivity to compounds 57 and 58 with MIC values of 170 and 330 µg·L−1, respectively. The effect of the compounds on membrane ergosterol was determined using an exogenous ergosterol assay, and the results showed that in the presence of exogenous ergosterol (MIC = 80 µg mL−1); the MIC value of compound 57 against C. albicans ATCC 10231 was enhanced 4-fold, indicating that the antifungal activity of compound 57 against C. albicans ATCC 10231 can be attributed to its effect on membrane ergosterol.
Evaluating posaconazole, its pharmacology, efficacy and safety for the prophylaxis and treatment of fungal infections
Published in Expert Opinion on Pharmacotherapy, 2022
Paraskevi Panagopoulou, Emmanuel Roilides
Ergosterol is an essential component of the fungal cell membrane, like cholesterol in human cells. It is synthesized from lanosterol by the action of lanosterol 14-α-demethylase (also known as CYP51A), a cytochrome P450 (CYP450)-dependent enzyme [13]. Posaconazole docks into the CYP51A and strongly inhibits it, by binding near the heme cofactor with the classic triazole and difluoro phenyl rings. In addition, it has a long side chain that stabilizes the bond especially in the presence of CYP51A mutations. This way it prevents demethylation at positions C-14 and/or C-4 of ergosterol precursors blocking its production [14–16]. This has two significant results: disruption of the functional integrity and increased permeability of the fungal cell membrane, and accumulation of methylated, toxic intermediaries and ergosterol precursors within the cells, leading to cell lysis [17]. In comparison to other azoles, posaconazole exhibits stronger inhibition of lanosterol 14-α-demethylase.