In addition, this agent may induce tumor cell apoptosis and. Simvastatin mik733, synvinolin and zocor is mainly obtained by semisynthetic process, involving the chemical modification of lovastatin side chain hoffman et al. Lovastatin is a fungal polyketide employed as a cholesterollowering drug that inhibits 3shydroxy3methylglutarylcoenzyme. Lovastatin information, side effects, warnings and recalls. Lovastatin biosynthesis by aspergillus terreus in a. Following administration of lovastatin tablets the coefficient of variation, based on betweensubject variability, was approximately 40% for the area under the curve. Indeed, lovastatin has been shown to interact synergis. Therapeutic class overview statins hmgcoa reductase. Lovastatin is indicated as an adjunct to diet for the reduction of elevated total c and ldlc levels in patients with primary hypercholesterolemia types iia and iib 2, when the response to diet restricted in saturated fat and cholesterol and to other nonpharmacological measures alone has been inadequate. Lovastatin c24h36o5 cid 53232 structure, chemical names, physical and.
Lovastatin definition of lovastatin by the free dictionary. Lovastatin is indicated as an adjunct to diet for the reduction of elevated totalc and ldlc levels in patients with primary hypercholesterolemia types iia and iib 2, when the response to diet. Lovastatin belongs to a group of drugs called hmgcoa reductase inhibitors, also known as statins. Hydrolyzed in vivo to an active metabolite, simvastatin. Muscle pain and stiffness in the shoulder, neck and pelvis. This makes lovastatin a promising drug to be administered. Simvastatin and lovastatin are lipophilic, while pravastatin is hydrophilic. Here we report the total synthesis of taxol by a convergent strategy, which opens a chemical pathway for the production of both the natural product itself and a variety of designed taxoids. The synthetic sequence is shown in the schemes below. Take lovastatin at around the same time s every day. Cholesterol is an organic compound, which is produced in humans by a complex metabolism.
Lovastatin is hydrolyzed to the active betahydroxyacid form, which competitively inhibits 3hydroxyl3methylgutarylcoenzyme a reductase, an enzyme involved in cholesterol biosynthesis. It acts as a precursor for the synthesis of many steroids, vitamin d. Dec 19, 2017 mevacor lovastatin is a cholesterollowering medication called a statin prescribed to treat elevated blood cholesterol levels. A major bulk of work in the synthesis of lovastatin was done by m. This new drug decreases cholesterol synthesis and apolipoprotein b concentrations, and increases ldl receptor activity without adverse effects on other products in the cholesterol pathway. Dietary butter was replaced by egg yolks in hypercholesterolaemic subjects treated with lovastatin mevinolin in order to record the effect of dietary cholesterol loading on serum. It works by decreasing the amount of cholesterol made in the body.
Some of these drug interactions with lovastatin may increase your risk for developing serious muscle problems see mevacor and muscle pain. Lovastatin is used along with a proper diet to help lower bad cholesterol and fats such as ldl, triglycerides and raise good cholesterol hdl in the blood. Lowering of total and ldl cholesterol and triglycerides. If used concomitantly, do not exceed lovastatin dosage of 40 mg. Lovastatin mevacor side effects, dosage, interactions. Nov 29, 2012 lovastatin is the first of a new class of cholesterol lowering drugs that competitively inhibit hmgcoa reductase. Synthesis there have been numerous approaches to the total synthesis of lovastatin 810. Lovastatin is used in adults and children who are at least 10 years old.
Simple organic reactions were used to get to lovastatin as shown in the scheme. All the statin molecules reduce the cholestrol level by same mechanism, where they inhibit the hmgcoa reductase, an important precursor in the cholesterol synthesis. Patchett, 1993, designed lovastatin 12 brenner et al. Lovastatin, sold under the brand name mevacor among others, is a statin medication, to treat high blood cholesterol and reduce the risk of cardiovascular disease. The initial derived mcr adduct can be considered as a synthetic hub to a vast diversity of other scaffolds. Mevacor should be used in addition to dietary modifications as part of a treatment plan to lower cholesterol levels when the response to diet and other nonpharmacological measures alone have been inadequate to reduce cardiovascu. Lovastatin, monacolin j, monacolin l, and mevastatin can be produced by monascus ruber, penicillium brevicompactum, and aspergillus terreus 1, 36. Both simvastatin and the active metabolite are strongly bound to plasma proteins 95%. Simvastatin is a lipidlowering agent derived synthetically from a fermentation product of the fungus aspergillus terreus. Research paper effects of lovastatin on mdamb231 breast. Simvastatin is indicated for the treatment of hyperlipidemia to reduce elevated total cholesterol totalc, lowdensity lipoprotein cholesterol ldl. Lovastatin increased highdensity lipoprotein hdl cholesterol levels 6%.
Compactin, ml236b and cs 500 has methyl butyric side chain r 1 and has only hydrogen group on r 2. This enzyme catalyzes the conversion of hmgcoa to mevalonate, which is a cholesterol precursor. The pharmacokinetic parameters in 12 hypercholesterolemic subjects at steady state, after 28 days of treatment, comparing altoprev 40 mg to lovastatin immediaterelease 40 mg, are summarized in. Pdf biosynthesis and biotechnological production of statins by. C, apolipoprotein b apo b, and triglycerides tg, and to increase highdensity lipoprotein cholesterol hdlc. Therapeutic class overview statins hmgcoa reductase inhibitors. Lovastatin may also be used for purposes not listed in this medication guide. Nov 11, 1988 a reduction in cholesterol synthesis by lovastatin has been subsequently confirmed in cell culture, animal studies and in humans. Hirama synthesized compactin and used one of the intermediates to. Lovastatin is used for the prevention of heart disease and the treatment of high cholesterol and high triglycerides. Lovastatin side effects, uses, dosage, overdose, pregnancy. Lovastatin mevacor is also one of the less potent of the statin class of medications, but its widely taken and generally well tolerated. Chemical transformations of lovastatin 2 into simvastatin 3.
Paralysis of some or all of the muscles of the eye. Lovastatin mevacor side effects, dosage, interactions drugs. A statin drug, c 24 h 36 o 5, that blocks the bodys. Inhibition of hmgcoa reductase decreases hepatic cholesterol synthesis, causing upregulation of lowdensity lipoprotein cholesterol ldlc receptors. Lovastatin is the first of a new class of cholesterol lowering drugs that competitively inhibit hmgcoa reductase. Lovastatin mevacor, marketed by merck under the brand name mevacor, was the first statin class medication ever to come out on the market in the 1980s. When used in combination with diet, weight loss, and exercise, lovastatin may reduce the risk of heart attack, stroke, and. It is also called as c6 hydroxyl analogue of mevastatin. The extendedrelease tablet usually is taken once a day at bedtime. Hirama synthesized compactin and used one of the intermediates to follow a different path to get to lovastatin.
Its available as a generic drug and as the brandname drug altoprev. The total synthesis of calcium atorvastatin request pdf. Atorvastatin lipitor by mcr acs medicinal chemistry letters. By controlling the rate of cholesterol production in the body, the medicine is effective in reducing total cholesterol, ldl cholesterol, and triglycerides, as well as increasing hdl cholesterol. All the statin molecules reduce the cholestrol level by same mechanism, where they inhibit the hmgcoa reductase, an important. Lovastatin oral tablet is a statin used to prevent and treat coronary heart disease, and to treat high cholesterol. May 24, 20 lovastatin belongs to a group of drugs called hmgcoa reductase inhibitors, also known as statins.
Lovastatin is a lactone metabolite isolated from the fungus aspergillus terreus with cholesterollowering and potential antineoplastic activities. Follow the directions on your prescription label carefully, and. Lovastatin was not detected in any of the raw puerh tea samples without storage but was found in almost all the ripe puerh tea samples, with lovastatin contents ranging from 20. It is an inactive prodrug, the methylated derivative of lovastatin, and like lovastatin, must be activated in the liver. Lovastatin 57 belongs to the family of statins, a class of compounds that are important cholesterol lowering drugs fig. The regular tablet usually is taken once or twice a day with meals. In patients with heterozygous familial or polygenic nonfamilial hypercholesterolaemia. There have been numerous approaches to the total synthesis of lovastatin. Our approach is based on an ugi reaction, which shortens the current synthetic route and is advantageous over the published syntheses. A resultant decrease in circulating total and lowdensity lipoprotein ldl cholesterol has also been demonstrated in animals and humans. Mevinolin, monacolin k and mevacor has methyl butyric side chain r 1 and 6a methyl group r 2. If used concomitantly, do not exceed lovastatin dosage of 40 mg daily. Feb 24, 2020 lovastatin is used to lower the risk of stroke, heart attack, and other heart complications in people with diabetes, coronary heart disease, or other risk factors.
Inhibits 3hydroxy3methylglutaryl coenzyme a hmg coa reductase, an enzyme which is responsible for catalyzing an early step in the synthesis of cholesterol. The synthesis of calcium atorvastatin 1 was performed using the remote 1,5anti asymmetric induction in the boronmediated aldol reaction of. This makes lovastatin a promising drug to be administered as a cytostatic agent in conjunction with other cytotoxic agents. Altoprev lovastatin extendedrelease tablets description. Lovastatin, sold under the brand name mevacor among others, is a statin medication, to treat. Lovastatin mevacor is a statin medication used to lower cholesterol. Microbial production and biomedical applications of lovastatin ncbi. Lovastatin is a fungal polyketide employed as a cholesterollowering drug that inhibits 3shydroxy3methylglutarylcoenzyme a hmgcoa reductase. Following administration of lovastatin tablets the coefficient of variation, based on betweensubject variability, was approximately 40% for the area under the curve auc of total inhibitory activity in the general circulation. F4655, f4658 this includes the treatment of primary hyperlipidemia fredrickson type iia, heterozygous familial and nonfamilial. Lovastatin mevacor, marketed by merck under the brand name mevacor, was the first statin class medication ever to come out on the. Zocor simvastatin dose, indications, adverse effects. The story of lipitor a peek into the world of pharmaceutical process chemistry aman desai 7th feb.
Here we report the total synthesis of taxol by a convergent strategy, which opens a chemical pathway for the production of both the natural product itself and a variety of designed. By controlling the rate of cholesterol production in the body, the medicine is. Atorvastatin lipitor by mcr acs medicinal chemistry. Avoid large quantities of grapefruit juice 1 qtday overdose management. The pharmacokinetic parameters in 12 hypercholesterolemic subjects. Lovastatin is used to lower the risk of stroke, heart attack, and other heart complications in people with diabetes, coronary heart disease, or other risk factors. This enzyme catalyses the synthesis of mevalonate, which is the immediate precursor of cholesterol and is the target of all of the drugs classed as statins. Increased risk of myopathy andor rhabdomyolysis 1 339. In filamentous fungi many secondary metabolites with complex chemical structure are synthesized via the polyketide pathway 15, 33, 37. Mevacor lovastatin is a cholesterollowering medication called a statin prescribed to treat elevated blood cholesterol levels. Thus, hmgcoa reductase inhibition by lovastatin at the therapeutic dose used here did not change the steadystate rate of wholebody cholesterol synthesis. Thus, the 1,4 amido acid motif could easily be derived from an ugi adduct with the. Figure 1 shows the synthesis of cholesterol from acetyl coa, and the inhibition. Lovastatin comes as a tablet and an extendedrelease longacting tablet to take by mouth.
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