An investigation into the mechanism of antihyperlipidemic action of 2-chloromethyl-5,6,7,8-tetrahydrobenzo(b)thieno[2,3-d]pyrimidin-4(3H)-one (LM-1554) was carried out through docking experiments with six different molecular targets; Niemann Pick C1 Like1 protein (NPC1L1), ATP citrate lyase (ACL), C-reactive protein (CRP), lanosterol 14α-demethylase (LDM), squalene synthase (SqS) and farnesiod X-receptor (FXR) known to be implicated in the physiology of hyperlipidemia. The interactions of LM-1554 were compared with the interactions of their respective co-crystallized native ligands at the active sites of these receptors. These comparisons are based on their docking parameters, as well as, types of interactions and vicinity with various amino acids in the active site pockets.
View Article and Find Full Text PDFHigh levels of cholesterol and other lipid constituents are major risk factors in the development of atherosclerosis as well as diseases and disorders associated with it. Though, drugs of various categories acting through different mechanisms are available for antihyperlipidemic therapy, there are limitations associated with each of them, keeping the interest in discovery of newer and better antihyperlipidemic drugs alive. Identification and exploitation of novel molecular targets for discovery of new antihyperlipidemic drugs is an important area of research.
View Article and Find Full Text PDFThe objective of this study was to develop self-emulsifying drug delivery system (SEDDS) to improve solubility and enhance the oral absorption of the poorly water-soluble drug, nevirapine. This lipid-based formulation may help to target the drug to lymphoid organs where HIV-1 virus resides mainly. The influence of the oil, surfactant and co-surfactant types on the drug solubility and their ratios on forming efficient and stable SEDDS were investigated in detail.
View Article and Find Full Text PDFAzetidin-2-ones, commonly referred as β-lactams, represent a unique ring system, with interesting chemistry and great biological potential. Besides its well known antibiotic activity, this ring system exhibits a wide range of activities, attracting the attention of researchers. The biological and pharmacological profile of azetidin-2-ones is reviewed here comprehensively with several examples under fourteen different activity heads.
View Article and Find Full Text PDFAlzheimer's disease (AD) is a progressive neurodegenerative disorder leading to irreversible loss of neurons, cognition and formation of abnormal protein aggregates. Rivastigmine, a reversible cholinesterase inhibitor used for the treatment of AD, undergoes extensive first-pass metabolism, thus limiting its absolute bioavailability to only 36% after 3-mg dose. Due to extreme aqueous solubility, rivastigmine shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing.
View Article and Find Full Text PDFJ Adv Pharm Technol Res
January 2011
A new oil-in-water microemulsion-based (ME) gel containing 1% itraconazole (ITZ) was developed for topical delivery. The solubility of ITZ in oils and surfactants was evaluated to identify potential excipients. The microemulsion existence ranges were defined through the construction of the pseudoternary phase diagrams.
View Article and Find Full Text PDFRifampicin, a first line anti-tubercular drug, has maximum solubility and permeability in the stomach. An oral multi-particulate formulation with site specific sustained delivery of rifampicin was developed. This oral gastroretentive rifampicin formulation consisted of rifampicin pellets for immediate release as the loading dose and a bio/mucoadhesive rifampicin tablet for extended release.
View Article and Find Full Text PDFLithium carbonate, a drug with narrow therapeutic index, needs therapeutic drug monitoring and dose adjustment to maintain lithium level within the therapeutic window. Conventional formulations of lithium carbonate exhibit immediate drug release causing swing/fluctuations in the plasma concentration of lithium, consequently leading to unfavorable side-effects and make dose adjustment difficult. The push-pull osmotic pump has been developed for zero order delivery of lithium carbonate for a period of 24 h.
View Article and Find Full Text PDFIn the present study, isoniazid was formulated as site-specific release pellets with high drug loading (65%, w/w) using extrusion-spheronization followed by aqueous coating of Sureteric (35% weight gain). A statistical experimental strategy was developed to optimize simultaneously the effect of the two formulation variables and one process variable on the critical physico-mechanical properties of the core pellets of isoniazid. Amount of granulating fluid and amount of binder were selected as formulation variables and spheronization speed as a process variable.
View Article and Find Full Text PDFA series of 5-carbethoxy-4-chloro-6-(substituted amino)pyrimidines was designed on the basis of its good 3-dimensional structural similarity with mefenamic acid (CAS 61-68-7), a well known anti-inflammatory drug. Synthesis of some 5-carbethoxy-4-chloro-6-(substitutedamino)pyrimidines has been achieved by cyclization of N-(cyanovinyl)formamidine intermediate in the presence of dry HCl. Target compounds were evaluated for their analgesic and anti-inflammatory potential by known experimental models.
View Article and Find Full Text PDFThe present work aims to predict drug release from novel site-specific release isoniazid pellets, in USP dissolution test apparatus 3, using the response surface methodology (RSM). Site-specific release isoniazid pellets were prepared by extrusion-spheronization followed by aqueous coating of Acryl-EZE. RSM was employed for designing of the experiment, generation of mathematical models and optimization study.
View Article and Find Full Text PDFSynthesis and antihyperlipidemic activity of a series of novel condensed 2-chloroalkyl-4-chloro/hydroxy-5,6-di-substituted pyrimidines are described. The design of these compounds is based on the earlier QSAR study on the antihyperlipidemic 2-substituted methylthienopyrimidin-4-ones. The newly synthesized condensed 4-chloro-2-chloroalkylpyrimidines (IIIa-n) have exhibited much superior antihyperlipidemic activity, compared to their earlier reported 4-hydroxy analogs.
View Article and Find Full Text PDFCoronary arterial diseases are responsible for more deaths than all other associated causes combined. Elevated serum cholesterol levels leading to atherosclerosis can cause coronary heart disease (CHD). Reduction in serum cholesterol levels reduces the risk for CHD, substantially.
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