Antimicrobial peptides (AMPs) hold promise as the next generation of antimicrobial agents, but often suffer from rapid degradation in vivo. Modifying AMPs with non-proteinogenic residues such as peptoids (oligomers of -alkylglycines) provides the potential to improve stability. We have identified two novel peptoid-based compounds, and , which are effective against the canine skin pathogen , the main cause of antibiotic use in companion animals. We report on their potential to treat infections topically by characterizing their release from formulation and in vitro ADME properties. In vitro ADME assays included skin penetration profiles, stability to proteases and liver microsomes, and plasma protein binding. Both and were resistant to proteases and >98% bound to plasma proteins. While half-lives in liver microsomes for both were >2 h, peptoid showed higher stability to plasma proteases than the peptide-peptoid hybrid B1 (>2 versus 0.5 h). Both compounds were suitable for administration in an oil-in-water cream formulation (50% release in 8 h), and displayed no skin permeation, in the absence or presence of skin permeability modifiers. Our results indicate that these peptoid-based drugs may be suitable as antimicrobials for local treatment of canine superficial pyoderma and that they can overcome the inherent limitations of stability encountered in peptides.
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http://dx.doi.org/10.3390/molecules23030630 | DOI Listing |
Chem Biol Drug Des
January 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
Target cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors; 5-([2,5-Dihydroxybenzyl]amino)salicylamides (Compounds 1-11) were examined for potential anticancer activity, with a trial to assess the underlying possible mechanisms. Compounds were assessed at a single dose against 60 cancer cell lines panel and those with the highest activity were tested in the five-dose assay. COMPARE analysis was conducted to explore potential mechanisms underlying their biological activity.
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January 2025
Department of Pharmacy, Faculty of Science, University of Rajshahi, Rajshahi, 6205, Bangladesh.
Heliotropium indicum is well-known for its diverse medicinal properties, traditionally utilized to treat ailments such as diabetes, obesity, bacterial infections, inflammation, and diarrhea. This study aims to explore the anti-inflammatory effects of the extract using in vitro methods and to assess its drug-likeness potential using docking, PASS and ADME. Fractionations of crude methanol extract (CME) were undertaken in n-hexane (NHF), chloroform (CHF), and ethyl acetate (EAF).
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January 2025
Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan.
A 3-dimensional (3D) cell culture is now being actively pursued to accomplish the in vivo-like cellular morphology and biological functions in cell culture. We recently obtained nano-fibrillated bacterial cellulose (NFBC). In this study, we developed a novel NFBC-based 3D cell-culture system, the OnGel method, and the Suspension method.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:
Intratumoral drug delivery systems hold immense promise in overcoming the limitations of conventional IV chemotherapy, particularly in enhancing therapeutic efficacy and minimizing systemic side effects. In this study, we introduce a novel redox-responsive intratumoral nanogel system that combines the biocompatibility of natural polysaccharides with the tailored properties of synthetic polymers. The nanogel features a unique cross-linked architecture incorporating redox-sensitive segments, designed to leverage the elevated glutathione levels in the tumor microenvironment for controlled drug release.
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January 2025
Preclinical Sciences & Translational Safety, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium. Electronic address:
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