Overriding Phthalate Decomposition When Exploring Mycophenolic Acid Intermediates as Selenium-Based ROS Biological Probes

: Paroxetine is a potent inhibitor of serotonin reuptake and is widely prescribed for the treatment of depression and other neurological disorders. The synthesis of paroxetine and the possibility to prepare derivatives with a specific substitution pattern that may allow their use as biological probes, is an attractive topic especially for medicinal chemists engaged in neurosciences research. Considering the extensive work that was developed in the last decade on the total synthesis of paroxetine, this review summarizes the most important contributions in this field, organized according to the reagent that was used as starting material. Most of the methods allowed to prepare paroxetine in 4-9 steps with an overall yield of 9-66%. Despite the progress made in this area, there is still room for improvement, searching for new eco-friendly and sustainable synthetic alternatives.

Download Full-text

Mycophenolic Acid Use in Glomerulonephritis

Letters in Drug Design & Discovery ◽

10.2174/157018006778194808 ◽

2006 ◽

Vol 3 (7) ◽

pp. 488-493

Author(s):

Elisabetta Bertoni ◽

Alessandra Stagnitto ◽

Silvia Farsetti ◽

Maurizio Salvadori

Keyword(s):

Mycophenolic Acid

Download Full-text

A Novel Curcumin-Mycophenolic Acid Conjugate Inhibited Hyperproliferation of Tumor Necrosis Factor-Alpha-Induced Human Keratinocyte Cells

Pharmaceutics ◽

10.3390/pharmaceutics13070956 ◽

2021 ◽

Vol 13 (7) ◽

pp. 956

Author(s):

Yonelian Yuyun ◽

Pahweenvaj Ratnatilaka Na Bhuket ◽

Wiwat Supasena ◽

Piyapan Suwattananuruk ◽

Kemika Praengam ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Mycophenolic Acid ◽

Tumor Necrosis ◽

Molecular Mechanisms ◽

Cellular Transport ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Anti Inflammatory ◽

Necrosis Factor

Curcumin (CUR) has been used as adjuvant therapy for therapeutic application in the treatment of psoriasis through several mechanisms of action. Due to the poor oral bioavailability of CUR, several approaches have been developed to overcome the limitations of CUR, including the prodrug strategy. In this study, CUR was esterified with mycophenolic acid (MPA) as a novel conjugate prodrug. The MPA-CUR conjugate was structurally elucidated using FT-IR, 1H-NMR, 13C-NMR, and MS techniques. Bioavailable fractions (BFs) across Caco-2 cells of CUR, MPA, and MPA-CUR were collected for further biological activity evaluation representing an in vitro cellular transport model for oral administration. The antipsoriatic effect of the BFs was determined using antiproliferation and anti-inflammation assays against hyperproliferation of tumor necrosis factor-alpha (TNF-α)-induced human keratinocytes (HaCaT). The BF of MPA-CUR provided better antiproliferation than that of CUR (p < 0.001). The enhanced hyperproliferation suppression of the BF of MPA-CUR resulted from the reduction of several inflammatory cytokines, including IL-6, IL-8, and IL-1β. The molecular mechanisms of anti-inflammatory activity were mediated by an attenuated signaling cascade of MAPKs protein, i.e., p38, ERK, and JNK. Our results present evidence for the MPA-CUR conjugate as a promising therapeutic agent for treating psoriasis by antiproliferative and anti-inflammatory actions.

Download Full-text

Mycophenolic Acid Exposure Prediction Using Machine Learning

Clinical Pharmacology & Therapeutics ◽

10.1002/cpt.2216 ◽

2021 ◽

Author(s):

Jean‐Baptiste Woillard ◽

Marc Labriffe ◽

Jean Debord ◽

Pierre Marquet

Keyword(s):

Machine Learning ◽

Mycophenolic Acid ◽

Acid Exposure

Download Full-text

A slow, efficient and safe nanoplatform of tailored ZnS QD-mycophenolic acid conjugates for in vitro drug delivery against dengue virus 2 genome replication

Nanoscale Advances ◽

10.1039/d0na00725k ◽

2020 ◽

Vol 2 (12) ◽

pp. 5777-5789

Author(s):

Ranjeet Dungdung ◽

Manikanta Bayal ◽

Lathika Valliyott ◽

Unnikrishnan Unniyampurath ◽

Swapna S. Nair ◽

...

Keyword(s):

Drug Delivery ◽

Dengue Virus ◽

Mycophenolic Acid ◽

Genome Replication ◽

Effective Delivery

The graphical abstract represents the synthesis of size engineered ZnS QDs for conjugating anti-viral drug (MPA) and its safe and effective delivery against cytoplasmically replicating dengue virus 2.

Download Full-text

ChemInform Abstract: DERIVATIVES OF MYCOPHENOLIC ACID

Chemischer Informationsdienst ◽

10.1002/chin.197821345 ◽

1978 ◽

Vol 9 (21) ◽

Author(s):

R. M. CARMAN

Keyword(s):

Mycophenolic Acid ◽

Derivatives Of

Download Full-text

Recombinant Peptide Mimetic NanoLuc Tracer for Sensitive Immunodetection of Mycophenolic Acid

Analytical Chemistry ◽

10.1021/acs.analchem.1c02109 ◽

2021 ◽

Author(s):

Álvaro Luque-Uría ◽

Riikka Peltomaa ◽

Tarja K. Nevanen ◽

Henri O. Arola ◽

Kristiina Iljin ◽

...

Keyword(s):

Mycophenolic Acid ◽

Recombinant Peptide ◽

Peptide Mimetic

Download Full-text

Pharmacokinetic Model Analysis of Supralingual, Oral and Intravenous Deliveries of Mycophenolic Acid

Pharmaceutics ◽

10.3390/pharmaceutics13040574 ◽

2021 ◽

Vol 13 (4) ◽

pp. 574

Author(s):

Xiuqing Gao ◽

Lei Wu ◽

Robert Y. L. Tsai ◽

Jing Ma ◽

Xiaohua Liu ◽

...

Keyword(s):

Oral Administration ◽

Mycophenolic Acid ◽

Systemic Circulation ◽

Sprague Dawley ◽

Anticancer Activities ◽

Sustained Drug Release ◽

Organ Rejection ◽

Patch Application ◽

Dorsal Tongue ◽

Tongue Surface

Mycophenolic acid (MPA) is commonly used for organ rejection prophylaxis via oral administration in the clinic. Recent studies have shown that MPA also has anticancer activities. To explore new therapeutic options for oral precancerous/cancerous lesions, MPA was designed to release topically on the dorsal tongue surface via a mucoadhesive patch. The objective of this study was to establish the pharmacokinetic (PK) and tongue tissue distribution of mucoadhesive MPA patch formulation after supralingual administration in rats and also compare the PK differences between oral, intravenous, and supralingual administration of MPA. Blood samples were collected from Sprague Dawley rats before and after a single intravenous bolus injection, a single oral dose, or a mucoadhesive patch administration on the dorsal tongue surface for 4 h, all with a dose of 0.5 mg/kg of MPA. Plots of MPA plasma concentration versus time were obtained. As multiple peaks were found in all three curves, the enterohepatic recycling (EHR) model in the Phoenix software was adapted to describe their PK parameters with an individual PK analysis method. The mean half-lives of intravenous and oral administrations were 10.5 h and 7.4 h, respectively. The estimated bioavailability after oral and supralingual administration was 72.4% and 7.6%, respectively. There was a 0.5 h lag-time presented after supralingual administration. The results suggest that the systemic plasma MPA concentrations were much lower in rats receiving supralingual administration compared to those receiving doses from the other two routes, and the amount of MPA accumulated in the tongue after patch application showed a sustained drug release pattern. Studies on the dynamic of drug retention in the tongue after supralingual administration showed that ~3.8% of the dose was accumulated inside of tongue right after the patch removal, ~0.11% of the dose remained after 20 h, and ~20.6% of MPA was not released from the patches 4 h after application. The data demonstrate that supralingual application of an MPA patch can deliver a high amount of drug at the site of administration with little systemic circulation exposure, hence lowering the potential gastrointestinal side effects associated with oral administration. Thus, supralingual administration is a potential alternative route for treating oral lesions.

Download Full-text