Topic
Lanosterol
About: Lanosterol is a research topic. Over the lifetime, 1239 publications have been published within this topic receiving 36737 citations. The topic is also known as: (3β)-lanosta-8,24-dien-3-ol & (3β,20R)-lanosta-8,24-dien-3-ol.
Papers published on a yearly basis
Papers
More filters
TL;DR: The results indicate the presence in rat intestine of enzyme systems involved in the saturation of the Δ24-bond in lanosterol and its metabolites, the conversion of 7-dehydrocholesterol into cholesterol, and those inhibited by SKF 525-A, which means the pathway of intestinal cholesterol synthesis is similar to that of the liver.
Abstract: SummaryAY-9944, SKF 525-A, triparanol, and 22,25-diazacholestanol, agents known to inhibit hepatic cholesterol synthesis, suppressed the incorporation of acetate-[2-14C] and mevalonate-[3H] into cholesterol by sections of everted rat intestines. Clofibrate had no effect on the conversion of acetate-[2-14C] into cholesterol. The results indicate the presence in rat intestine of enzyme systems involved in the saturation of the Δ24-bond in lanosterol and its metabolites, the conversion of 7-dehydrocholesterol into cholesterol, and those inhibited by SKF 525-A. Hence, the pathway of intestinal cholesterol synthesis is similar to that of the liver.
6 citations
TL;DR: In the present investigation, the efficiency of AA was effectively proved through the in vitro and in silico analysis and evidenced the effectiveness of AA as a potential candidate against C. albicans.
Abstract: Antibiotic resistance is one of the major concerns and the biggest threats to the world population. The incidents of antibiotic resistance in Candida spp. were frequently recorded. In the present investigation, antifungal potential of ascorbic acid (AA) was evaluated. According to the in vitro analysis, the zone of inhibition of AA (24.75 ± 0.35 mm) against C. albicans was greater as compared to other vitamins tested. AA significantly modulate the growth of C. albicans at 25 mg/ml. The highest percentage (94.67%) of cell viability was observed in untreated cells, and low cell viability (29.36%) was observed in cells treated with 50 mg/ml of AA (2 × MIC). Further, AO/EB (acridine orange/ethidium bromide), propidium iodide staining, and real-time qPCR confirmed the loss of membrane integrity due to membrane lesions that caused cell death. Lanosterol 14-α-demethylase (L-14α-DM) is the product of ERG11 and acted as superior drug target of C. albicans. Molecular docking analysis confirmed that active interaction of ascorbic acid with L-14α-DM. Based on the present investigation, the efficiency of AA was effectively proved through the in vitro and in silico analysis. This finding has evidenced the effectiveness of AA as a potential candidate against C. albicans.
6 citations
TL;DR: The results indicate that α-methyl γ-phenyl butyric acid probably affects some of the enzymic reactions which convert acetate into mevalonate and meval onate into squalene, without influencing successive metabolic steps.
6 citations
05 Aug 2021
TL;DR: In this article, the authors have prepared and characterized four organometallic derivatives of the frontline antifungal drug fluconazole (1a, 4a), and showed that 2a is active in vivo with added activity on the host innate immune response.
Abstract: Fungal infections represent a global problem, notably for immunocompromised patients in hospital, COVID-19 patient wards and care home settings, and the ever-increasing emergence of multidrug resistant fungal strains is a sword of Damocles hanging over many healthcare systems. Azoles represent the mainstay of antifungal drugs, and their mode of action involves the binding mode of these molecules to the fungal lanosterol 14α-demethylase target enzyme. In this study, we have prepared and characterized four novel organometallic derivatives of the frontline antifungal drug fluconazole (1a–4a). Very importantly, enzyme inhibition and chemogenomic profiling demonstrated that lanosterol 14α-demethylase, as for fluconazole, was the main target of the most active compound of the series, (N-(ferrocenylmethyl)-2-(2,4-difluorophenyl)-2-hydroxy-N-methyl-3-(1H-1,2,4-triazol-1-yl)propan-1-aminium chloride, 2a). Transmission electron microscopy (TEM) studies suggested that 2a induced a loss in cell wall integrity as well as intracellular features ascribable to late apoptosis or necrosis. The impressive activity of 2a was further confirmed on clinical isolates, where antimycotic potency up to 400 times higher than fluconazole was observed. Also, 2a showed activity towards azole-resistant strains. This finding is very interesting since the primary target of 2a is the same as that of fluconazole, emphasizing the role played by the organometallic moiety. In vivo experiments in a mice model of Candida infections revealed that 2a reduced the fungal growth and dissemination but also ameliorated immunopathology, a finding suggesting that 2a is active in vivo with added activity on the host innate immune response.
6 citations
TL;DR: In vitro incorporation of sodium acetate-3H or DL-mevalonic acid-2-14C into cholesterol was markedly increased in the liver homogenates from a patient with hypercholesterolemia, but it showed no difference between the patient and controls when skin, adipose tissue, bone marrow cells or leukocytes were used.
Abstract: In two cases of idiopathic hypercholesterolemia, aged 6 and 12 years, it was found that in vivo incorporation of sodium acetate-1-14C into serum cholesterol was markedly increased, but that into squalene and lanosterol in serum was less than that in controls. In vitro incorporation of sodium acetate-3H or DL-mevalonic acid-2-14C into cholesterol was markedly increased in the liver homogenates from a patient with hypercholesterolemia, but it showed no difference between the patient and controls when skin, adipose tissue, bone marrow cells or leukocytes were used.
6 citations