As an approach to discovering highly potent motilides with oral activity, novel 4"-deoxy derivatives of 8,9-anhydroerythromycin 6,9-hemiacetal were designed, synthesized, and evaluated for their gastrointestinal prokinetic activities. These compounds were orders of magnitude more potent than their 4"-hydroxy analogs in inducing smooth muscle contractions in an in vitro rabbit duodenal assay. Removal of the 12-hydroxy group, which was aimed at improving oral bioavailability, also afforded further potentiation in in vitro activity, leading to the identification of 8,9-anhydro-4"-deoxy-3'-N-desmethyl-3'-N-ethylerythromycin B 6,9-hemiacetal (ABT-229) as a potential prokinetic drug. ABT-229 was > 300,000 times more potent than erythromycin in vitro and had 39% oral bioavailability in dog compared to its 4",12-dihydroxy congener (EM-523), which was only 400 times more potent than erythromycin and had relatively low (1.4%) oral bioavailability.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm00010a024 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Solid Self-Microemulsifying Drug Delivery System for Improved Oral Bioavailability of Relugolix: Preparation and Evaluation.
Int J Nanomedicine
January 2025
School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People's Republic of China.
Purpose: To improve the oral absorption of relugolix (RLGL), which has low oral bioavailability due to its low solubility and being a substrate of P-glycoprotein (P-gp). A solid self-microemulsifying drug delivery system of relugolix (RLGL-S-SMEDDS) was prepared and evaluated in vitro and in vivo.
Methods: The composition of the solid self-microemulsifying drug delivery system (S-SMEDDS) was selected by solubility study and pseudo-ternary phase diagram, and further optimized by Design-Expert optimization design.
Study of antiplasmodial activity, toxicity, pharmacokinetic profiles of n-methyl-isatin (CHISACN) derivative.
Exp Parasitol
January 2025
Post-graduate Program in Studies in Natural Products and Synthetic Bioactive, Federal University of Paraíba, João Pessoa, PB, Brazil; Laboratory of Toxicological Tests, Federal University of Paraíba, João Pessoa, PB, Brazil; Post-graduate Program in Studies in Development and Technological Innovation in Medicines, Federal University of Paraíba, João Pessoa, PB, Brazil.
One of the main factors that have made it difficult to control malaria is the large number of parasites that are resistant to the usual antimalarial drugs. Therefore, the development of new drugs that are more effective and with low toxicity for humans is necessary. In this work, we evaluated the adduct 2-(3-hydroxy-1-methyl-2-oxoindolin-3-yl) acrylonitrile, also called CHISACN, as a potential antimalarial through in vitro studies, and evaluated its effects in silico and in vivo toxicology.
View Article and Find Full Text PDFThe role of green synthesis metal and metal oxide nanoparticles in oral cancer therapy: a review.
J Drug Target
January 2025
School of Stomatology, Wannan Medical College, Wuhu 241000, Anhui, China.
There are 275,000 new cases of oral cancer (OC) per year, making it the sixth most common cancer in the world. Severe adverse effects, including loss of function, deformity, and systemic toxicity, are familiar with traditional therapies such as radiation, chemotherapy, and surgery; due to their unique properties, nanoparticles (NPs) have emerged as a superior alternative over chemo/radiotherapy and surgery due to their targeting capability, bioavailability, compatibility, and high solubility. Due to their unique properties, metallic NPs have garnered significant attention in OC control.
View Article and Find Full Text PDFCopaiba essential oil carried in a self-nanoemulsifying drug delivery system improves adjuvant-induced arthritis in rats.
J Pharm Pharmacol
January 2025
Department of Biochemistry, State University of Maringá, 87020900, PR, Brazil.
Objectives: Copaiba essential oil (CEO) is obtained through the distillation of copaiba balsam and has been used in the traditional medicine to treat inflammatory conditions. However, the highly lipophilic nature of CEO restricts its pharmaceutical use. This study evaluated the effect of CEO, carried in a self-nanoemulsifying drug delivery system (SNEDDS), on articular and systemic inflammation and liver changes in Holtzman rats with Freund's adjuvant-induced arthritis.
View Article and Find Full Text PDFEffects of vitamin D and L-cysteine cosupplementation on circulating bioavailable and total 25-hydroxy-vitamin D, the free/total testosterone ratio and inflammatory biomarkers in healthy vitamin D-deficient African Americans: a placebo-controlled double-blind clinical trial.
BMJ Nutr Prev Health
August 2024
Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Background: Subjects with metabolic syndrome and obesity have higher levels of inflammation with depression of the vitamin D (VD) hydroxylase/metabolising genes () required to convert VD consumed in the diet into 25(OH)VD. Compared with total 25(OH)VD levels, measurement of bioavailable 25(OH)VD is a better method to determine the beneficial effect of VD.
Objective: This study investigates whether cosupplementation with VD and L-cysteine (LC), which downregulates inflammation and upregulates VD-regulating genes, provides a better therapeutic benefit than supplementation with VD-alone in African Americans (AA).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!