sterol biosynthesis

Naftifine Hydrochloride is the hydrochloride salt form of naftifine, an allylamine derivate with synthetic broad-spectrum antifungal activity. Although the exact mechanism through which naftifine hydrochloride exerts its effect is unknown, it appears to selectively inhibit the enzyme squalene 2, 3-epoxidase, thereby inhibiting the biosynthesis of sterol. This results in a decreased amount of sterols, especially ergosterol which is the primary fungal membrane sterol, and a corresponding accumulation of squalene in fungal cells. Naftifine hydrochloride (Naftifine HCl) can be fungicidal as well as fungistatic to yeasts depending on the concentration and the organisms involved.

Uniconazole is a plant growth regulator that inhibit cytochrome P450 707As (Ki=68 nM). CYP707As is a major ABA catabolic enzyme that catabolize Abscisic acid, accordingly suppress gibberellin and sterol biosynthesis.

Clotrimazole (FB 5097), an imidazole derivative with a broad spectrum of antimycotic activity, inhibits biosynthesis of the sterol ergostol.

AY 9944 is a specific cholesterol biosynthesis inhibitor that targets the 7-dehydrocholesterol Δ7-reductase (DHCR7) enzyme (IC50=13 nM). At high doses, AY 9944 also inhibits sterol Δ7-Δ8 isomerase in cultured embryos, leading to the accumulation of cholest-8-en-3β-ol[1][2][3]. Additionally, AY 9944 causes hypocholesterolemia and accumulation of 7DHC.

25-Hydroxycholesterol is a steroid derivative that suppresses the cleavage of sterol regulatory element binding proteins (SREBPs). It inhibits HMG-CoA reductase and so it also plays a significant role in the in vivo regulation of cholesterol biosynthesis

Peraclopone is a hypolidemic drug. It is an inhibitor of 7-Dehydrocholesterol reductase. Peraclopone potently inhibits the final step in cholesterol biosynthesis. Feeding this agent to rats leads to a rapid replacement of membrane cholesterol with its immediate precursor 7-dehydrocholesterol, and a dramatic reduction in plasma sterol concentration. Peraclopone caused a dose-dependent decrease in cholesterol and a concomitant accumulation of provitamin D3 (7-dehydrocholesterol) in the skin, which is accompanied by an increase in the plasma level of 25-hydroxyvitamin D3. Treatment with peraclopone dramatically alters membrane sterol content in many membranes including the microvillus membrane of both the jejunum and ileum. In the jejunal microvillus membrane a major change in chemical composition occurred, presumably in response to the alteration in membrane sterol. The net result was a significant decline in both the static and dynamic component of membrane fluidity.

Fenhexamid (Elevate), a sterol biosynthesis inhibitor, shows antifungal activity against the plant pathogenic fungus. Fenhexamid is used for agriculture and is present in measurable amounts in fruits and vegetables.

Dimethomorph is a morpholine fungicide belonging to the fungicide group of sterol biosynthesis inhibitors that inhibits fungal cell wall formation. Dimethomorph inhibits mycelial growth of the oomycete fungi, P. citrophthora, P. parasitica, P. capsici, and P. infestans ( EC 50 s=0.1, 0.38, <0.1, and 0.16-0.3 μg/mL, respectively), but is less active against the green algae species C. vulgaris or S. obliquus in vitro (EC 50 s=47.46 and 44.87 μg/mL, respectively). Dimethomorph inhibits androgen receptor (AR) activity in a reporter assay in MDA-kb2 human breast cancer cells but not in a yeast antiandrogen screen ( IC 20 s=0.263 and 38.5 μM, respectively).

(Z)-Lanoconazole is the Z configuration of Lanoconazole, used for investigating dermatophytosis and onychomycosis. It inhibits sterol 14-alpha demethylase, disrupting fungal membrane ergosterol biosynthesis. Lanoconazole is a potent, orally active imidazole antifungal agent with a broad spectrum of activity against fungi both in vitro and in vivo [1] [2].

Steryl glucosides are neutral glycolipids commonly found in plant cell membranes and vegetable oils that contain a glucose moiety conjugated to a sterol lipid. They function as glucose donors in the biosynthesis of glucocerebrosides in plant microsomes and are metabolic precursors to acylated/esterified steryl glucosides. Steryl glucosides are the major component of filter- and engine-damaging precipitates formed during biodiesel production from transesterification of vegetable oils. This product contains a mixture of steryl glucosides.

Cyclopentanol is a plant sterol compound and one of the key precursors for biosynthesis of various sterol compounds. Cycloartenol inhibits the migration of glioma cells and inhibits the phosphorylation of p38 MAP kinase. Cycloenol has various pharmacologi

Fenpropidin (Ro-12-3049), a fungicide, is a specific inhibitor of sterol 14-reductase and biosynthesis.

Pregnanetriol is a metabolite of 17α-hydroxyprogesterone .1,2It is formed from 17α-hydroxyprogesterone by reduction of the C-20 ketone.2Urinary levels of pregnanetriol are elevated in patients with 21-hydroxylase deficiency and congenital adrenal hyperplasia.3,4 1.Kamrath, C., Hartmann, M.F., Boettcher, C., et al.Diagnosis of 21-hydroxylase deficiency by urinary metabolite ratios using gas chromatography-mass spectrometry analysis: Reference values for neonates and infantsJ. Steroid Biochem. Mol. Biol.15610-16(2016) 2.Schiffer, L., Barnard, L., Baranowski, E.S., et al.Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: A comprehensive reviewJ. Steroid Biochem. Mol. Biol.194105439(2019) 3.Disorders of steroidogenesis guide to steroid profiling and biochemical diagnosis1(2019) 4.Shackleton, C.H.L.Role of a disordered steroid metabolome in the elucidation of sterol and steroid biosynthesisLipids47(1)1-12(2012)

Lanoconazole is an orally active imidazole antifungal agent that displays a broad spectrum of activity against fungi in vitro and in vivo. Lanoconazole interferes with ergosterol biosynthesis by inhibiting sterol 14-alpha demethylase and blocking fungal membrane ergosterol biosynthesis.

Penconazole is a typical triazole fungicide, which mainly used to control powdery mildew in apples, grapes, and vegetables. Penconazole inhibits sterol biosynthesis in fungi. Penconazole decrease AChE activity in the cerebrum and cerebellum of rats [1] [2].

The compound binds and blocks farnesyl diphosphate synthase in the HMG-CoA pathway (IC50 = 460 nM for recombinant human FPPS). It causes macrophage apoptosis and inhibits prenylation and sterol biosynthesis in purified osteoclasts.