Dataset Information

Fluorocurcumins as cyclooxygenase-2 inhibitor: molecular docking, pharmacokinetics and tissue distribution in mice.

ABSTRACT: The purpose of the current study was to assess the effect of newly synthesized Curcumin analogs on COX-2 protein by molecular docking studies and by assessments of the effect of one such analog (CDF) on nuclear factor NF-kappaB and PGE(2). In addition, we have determined the pharmacokinetics and tissue distribution of CDF in mice compared to Curcumin.Molecular docking on COX-2 protein was assessed by standard computer modeling studies. PGE(2) assay in conditioned media was done utilizing high sensitivity immunoassay kit following manufacturer's instructions, while NF-kappaB was done by routine EMSA. Serum pharmacokinetics and tissue distribution studies were carried out using the validated high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) methods.The molecular docking showed that fluorocurcumin analogs do not introduce any major steric changes compared to the parent Curcumin molecule, which was consistent with down-regulation of NF-kappaB and reduced PGE(2) levels in cells treated with CDF. Pharmacokinetic parameters revealed that CDF had better retention and bioavailability and that the concentration of CDF in the pancreas tissue was 10-fold higher compared to Curcumin.Our observations clearly suggest that the bioavailability of CDF is much superior compared to Curcumin, suggesting that CDF would be clinically useful.

SUBMITTER: Padhye S

PROVIDER: S-EPMC3759818 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fluorocurcumins as cyclooxygenase-2 inhibitor: molecular docking, pharmacokinetics and tissue distribution in mice.

Padhye Subhash S Banerjee Sanjeev S Chavan Deepak D Pandye Shubhangini S Swamy K Venkateswara KV Ali Shadan S Li Jing J Dou Q Ping QP Sarkar Fazlul H FH

Pharmaceutical research 20090828 11

<h4>Purpose</h4>The purpose of the current study was to assess the effect of newly synthesized Curcumin analogs on COX-2 protein by molecular docking studies and by assessments of the effect of one such analog (CDF) on nuclear factor NF-kappaB and PGE(2). In addition, we have determined the pharmacokinetics and tissue distribution of CDF in mice compared to Curcumin.<h4>Methods</h4>Molecular docking on COX-2 protein was assessed by standard computer modeling studies. PGE(2) assay in conditioned ...[more]

PMID: 19714451

Similar Datasets

Project description:Eravacycline (7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline or TP-434) is a novel, fully synthetic broad-spectrum fluorocycline with potent activity against Gram-positive bacteria, anaerobes, and multidrug-resistant Enterobacteriaceae We characterized the plasma pharmacokinetics of eravacycline and conducted a comprehensive analysis of the eravacycline tissue distribution in rabbits after multiple-day dosing. For single-dose pharmacokinetic analysis, eravacycline was administered to New Zealand White (NZW) rabbits at 1, 2, 4, 8, and 10 mg/kg of body weight intravenously (i.v.) once a day (QD) (n = 20). For multidose pharmacokinetic analysis, eravacycline was administered at 0.5, 1, 2, and 4 mg/kg i.v. QD (n = 20) for 6 days. Eravacycline concentrations in plasma and tissues were analyzed by a liquid chromatography-tandem mass spectrometry assay. Mean areas under the concentration-time curves (AUCs) following a single eravacycline dose ranged from 5.39 ?g · h/ml to 183.53 ?g · h/ml. Within the multidose study, mean AUCs ranged from 2.53 ?g · h/ml to 29.89 ?g · h/ml. AUCs correlated linearly within the dosage range (r = 0.97; P = 0.0001). In the cardiopulmonary system, the concentrations were the highest in the lung, followed by the heart > pulmonary alveolar macrophages > bronchoalveolar lavage fluid; for the intra-abdominal system, the concentrations were the highest in bile, followed by the liver > gallbladder > spleen > pancreas; for the renal system, the concentrations were the highest in urine, followed by those in the renal cortex > renal medulla; for the musculoskeletal tissues, the concentrations were the highest in muscle psoas, followed by those in the bone marrow > adipose tissue; for the central nervous system, the concentrations were the highest in cerebrum, followed by those in the aqueous humor > cerebrospinal fluid > choroid > vitreous. The prostate and seminal vesicles demonstrated relatively high mean concentrations. The plasma pharmacokinetic profile of 0.5 to 4 mg/kg in NZW rabbits yields an exposure comparable to that in humans (1 or 2 mg/kg every 12 h) and demonstrates target tissue concentrations in most sites.

Dataset Information

Fluorocurcumins as cyclooxygenase-2 inhibitor: molecular docking, pharmacokinetics and tissue distribution in mice.

Publications

Fluorocurcumins as cyclooxygenase-2 inhibitor: molecular docking, pharmacokinetics and tissue distribution in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets