Drugs and Drug Candidates

Background/Objectives: Recent reports have demonstrated the antiparasitic activity of 1,4-dihydropyridine (1,4-DHPs). This study aimed to assess the in vitro antischistosomal activity of 24 1,4-DHPs against Schistosoma mansoni adult worms. Methods: Sixteen hexahydroquinolines (1–16) and eight Hantzsch esters (17–24) previously obtained through a multicomponent Hantzsch reaction were tested in vitro against Schistosoma mansoni adult worms. In silico studies with the most active compounds were also carried out. Results: Among the tested compounds, the Hantzsch esters 20 (diethyl 4-(4-bromophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) and 21 (diethyl 4-(3-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) provided the lowest IC₅₀ (15.2 and 13.1 µM, respectively) and the highest selectivity for this parasite (SI = 2.31 and >4.59, respectively). Conclusions: Docking studies revealed that compound 21 has a high affinity for the S. mansoni target (PDB ID: 6UY4). Furthermore, ADMET predictions indicated that compound 21 meets the drug-likeness criteria without violating any Lipinski, Veber, or Egan’s rules.

In the published manuscript [...]

Background/Objectives: Periodontal disease is a condition marked by the destruction of tooth-supporting tissues, driven by an exaggerated immune response to an unbalanced dental biofilm. Conventional treatments struggle due to antimicrobial resistance and the biofilm’s protective extracellular matrix. This study evaluates the potential of bacteriophages as an innovative strategy for managing periodontal disease. Methods: This research employed a qualitative approach using Discursive Textual Analysis, with IRAMUTEQ version 0.8 alpha 7 (Interface de R pour les Analyses Multidimensionnelles de Textes et de Questionnaires) software. The search was conducted in the Orbit Intelligence and PubMed databases, for patents and scholarly articles, respectively. The textual data underwent Descending Hierarchical Classification, Correspondence Factor Analysis, and Similarity Analysis to identify core themes and relationships between words. Results: The analysis revealed an increase in research and patent filings concerning phage therapy for periodontal disease since 2017, emphasizing its market potential. The primary centers for intellectual property activity were identified as China and the United States. The study identified five focus areas: Genomic/Structural Characterization, Patent Formulations, Etiology, Therapeutic Efficacy, and Ecology/Phage Interactions. Lytic phages were shown to be effective against prominent pathogens such as Fusobacterium nucleatum and Enterococcus faecalis. Conversely, the lysogenic phages poses a potential risk, as they may transfer resistance and virulence factors, enhancing pathogenicity. Conclusions: Phage therapy is a promising approach to address antimicrobial resistance and biofilm challenges in periodontitis management. Key challenges include the need for the clinical validation of formulations and stable delivery systems for the subgingival area. Future strategies, such as phage genetic engineering and data-driven cocktail design, are crucial for enhancing efficacy and overcoming regulatory hurdles.