Background: Oral squamous cell carcinoma (OSCC) is an aggressive cancer closely associated with smoking and alcohol consumption, with a higher incidence in men. Despite changes in treatment strategies, poor survival persists in most patients, highlighting the need for novel and improved therapeutic options. Naphthoquinone analogs are being investigated because of their active redox structure and broad pharmacological profile; they demonstrate cytotoxic antitumor activity, making them potential candidates for new drug agents. Objective: This study investigated new benzyl-naphthoquinone compounds as potential anticancer agents for various genotypes of oral squamous cell carcinoma (OSCC) and other cancer cells. Methods: This study reports the synthesis and evaluation of a series of eight benzyl-naphthoquinone compounds against oral squamous cell carcinoma. Results: Four compounds 1–4 showed the best cytotoxic profiles, with a selectivity index ≥ 3 for all OSCC cell lines tested. Compound 1 was the most selective compound in all OSCC models, showing a higher selectivity index than both carboplatin and shikonin. Furthermore, compound 1 induced DNA fragmentation, cell-cycle arrest, and caspase-3/7 activation, changes consistent with apoptosis, and time-lapse imaging corroborated the apoptotic phenotype. Hemolysis assays showed minimal toxicity in human erythrocytes, and acute in vivo evaluation in mice revealed no evident adverse effects under the conditions tested, indicating low acute toxicity, although more detailed histopathological and biochemical studies will be required to fully establish the safety profile. Molecular modeling suggested that compound 1 may interact with topoisomerase II, RSK2, and PKM2, which could contribute to the activation of apoptotic pathways, although these interactions remain predictive and require biochemical validation. Finally, in silico analysis of physicochemical and ADMET parameters indicated properties compatible with oral absorption and systemic exposure, together with predicted low toxicity; however, these results are model-based and should be confirmed experimentally. Conclusions: Based on these findings, compound 1 emerges as a promising lead candidate for the development of a novel chemotherapeutic agent against OSCC, with potential therapeutic efficacy against other cancer types.

Chemotherapy, one of the primary cancer treatments, has a high risk of causing significant harm in cases of its misuse. Pharmaceutical intervention is one of the strategies used to prevent medication errors from reaching the patient by identifying drug-related problems or other discrepancies related to patient data or medical progress. The primary objective of this study was to analyze the profile of the pharmaceutical intervention made in chemotherapy prescriptions for adult and pediatric patients in order to measure its impact on patient safety. A retrospective cross-sectional and observational study was conducted at a reference center for cancer treatment in Rio de Janeiro, Brazil. Pharmaceutical interventions performed in chemotherapy prescriptions from January to October 2022 were quantified, classified, and analyzed by their type, most common medicine, and acceptability. From the patients treated in the period, 220 (14.8%) adults and 64 (23.4%) children and teenagers received at least one pharmaceutical intervention. The most common types for adults were dose adjustments: overdose (22.5%) and underdose (22.5%). However, in pediatry, incompleteness of supporting drug protocol (22.1%) was the most registered. The most common medicines involved in pharmaceutical intervention were carboplatin (for adults) and electrolytes/hydration (for pediatric patients). Pharmaceutical intervention acceptability by prescriptors was very similar, reaching 80.4% for adults and 77.9% for pediatrics. The pharmaceutical intervention profile was quite distinct by virtue of the singularities of each population. The pharmacists’ role was shown to be paramount in intercepting medication errors in the prescription of chemotherapy protocols, contributing to patient safety.