Current Topics in Medicinal Chemistry - Volume 25, Issue 14, 2025

Failures of osseointegrated implants pose significant challenges in the medical field, often due to prolonged osseointegration periods and bacterial infections. Functionalization of Titanium Dioxide Nanotubes (TNTs) has emerged as a promising strategy to improve osseointegration and mitigate infections. This study aims to conduct a bibliometric analysis and review to identify trends, gaps, and advancements in research on the functionalization of TNTs for osseointegration improvement.

Articles were retrieved from the Web of Science database using the keywords “osseointegration,” “titanium dioxide nanotubes,” and “functionalization.” The inclusion criteria were studies published between 2014 and 2023, written in English, and focusing on the use of TNTs in implant surface modifications. A total of 126 articles were included after screening. Data extraction and analysis were performed using VOS Viewer, Microsoft Excel, and GraphPad Prism.

The review revealed a growing number of publications on TNTs functionalization, with China, the United States, and Brazil leading in contributions. Key findings include the effectiveness of TNTs loaded with bioactive agents (e.g., silver, strontium, hydroxyapatite) in promoting osseointegration and antibacterial activity. Collaborative networks among institutions and authors were mapped, highlighting the Sao Paulo State University and Yong Huang as the most prolific contributors.

The findings underscore the potential of TNTs functionalization to enhance implant performance. However, a gap remains in translating preclinical findings into clinical trials. Future research should focus on clinical validation to bridge this gap and translate laboratory advancements into therapeutic solutions.

Zika (ZIKV) is a virus transmitted by mosquitoes that can cause Guillain-Barré syndrome and congenital malformations like microcephaly. Given its explosive resurgence and the resulting epidemics in 2016, the search for effective antiviral drugs has become absolutely necessary.

In this study, we examined the potential of naphthoquinone derivatives that have a sulfonamide or sulfonate group to inhibit ZIKV replication in primary cultured neurons and in Vero cells.

In our in vitro studies, we found that PAV05 had low cytotoxicity with a CC50 of 329 µM ±3.6 for Vero cells and 290 µM ±3.5 for neurons. Additionally, we observed a strong inhibitory activity on viral replication with an EC50 value of EC50 of 0.92 µM ±0.15 in Vero cells, resulting in a Selectivity Index (SI) of 357. Even when added 16 hours post-infection, PAV05 maintained its inhibitory effect. When PAV05 was evaluated in sub-optimal concentrations together with Ribavirin, we observed a strong synergistic effect, with an inhibition greater than 90% even at doses of 0.5 µM. In silico tests suggested that PAV05 may have effects on ZIKV NS2B-NS3.

The ZIKV inhibitor described in this study shows promise as a compound for the development of therapies against ZIKV. It may also be considered for inclusion in the portfolio of broad-spectrum antiflavivirus inhibitors.

The search for new antifungal agents is critical due to the rising resistance of fungal pathogens to existing treatments. This study focuses on the synthesis and evaluation of a novel compound, 1-benzyl-5-methyl-1H-pyrazole-3-carboxylic acid (compound L1), as a potential antifungal agent.

Compound L1 was synthesized and characterized using a range of analytical techniques, including 1H^1H1H NMR, 13C^{13}C13C NMR, FT-IR, GC-MS, and X-ray single crystal diffraction (XRD). The antifungal activity of the compound was assessed in vitro, and its molecular structure was studied using Density Functional Theory (DFT). Molecular docking and dynamics simulations were conducted to evaluate the interaction of the compound with sterol 14-alpha demethylase (CYP51) from Candida albicans. ADME/Tox evaluations were also performed to assess the drug-like properties of compound L1.

Compound L1 exhibited moderate antifungal activity with an IC50 value of 34.25 µg/mL. DFT studies confirmed the highly stable molecular structure of the compound. Molecular docking and dynamics simulations demonstrated that compound L1 had a higher affinity and stability when forming complexes with the crystal structure of CYP51, particularly in interaction with the tetrazole-based antifungal drug candidate VT1161 (PDB ID: 5TZ1). ADME/Tox evaluations indicated favorable drug-like properties for compound L1.

The results suggest that compound L1 is a promising antifungal candidate, showing greater potential than fluconazole in the conducted evaluations. Further studies are warranted to explore its full therapeutic potential.

The increasing prevalence of drug-resistant bacterial infections poses a significant challenge to global healthcare, necessitating the development of novel antibacterial agents. Coumarin-based derivatives are well-recognized for their diverse biological activities, and hybridization with other pharmacophores offers a promising strategy for enhancing therapeutic efficacy and overcoming resistance.

This study aimed to synthesize and evaluate a novel series of coumarin hybrids by integrating the coumarin scaffold with sulfanilamide (9a-e) and 2-aminobenzothiazole (10a-e), targeting bacterial pathogens through a dual pharmacophoric approach.

The synthesized hybrids were characterized using mass spectrometry, FTIR, and NMR (¹H and ¹³C) to confirm their structural integrity. Antibacterial activity was assessed in vitro against Escherichia coli and Staphylococcus aureus at concentrations of 100, 250, and 500 µg/ml, with ciprofloxacin as the standard. The molecular binding mechanism was explored using molecular docking and pharmacophore-based analysis.

Among the synthesized derivatives, compounds 9e and 10e exhibited the highest antibacterial activity, with inhibition zones of 22 mm and 21 mm against E. coli and 25 mm and 22 mm against S. aureus at 500 µg/ml, demonstrating comparable efficacy to ciprofloxacin. Molecular docking studies revealed strong interactions of these compounds with bacterial enzymes, supporting the in vitro results and highlighting their potential as protein-inhibitor candidates.

The novel hybrid derivatives demonstrated significant antibacterial activities, suggesting their potential as promising therapeutic agents. Their effectiveness against various bacterial strains indicated that these compounds could serve as a foundation for the development of new antibacterial drugs. Further research and optimization are needed to enhance their potency and ensure their safety, paving the way for future clinical applications.