Introduction: Thrombotic disorders are among the leading causes of morbidity and mortality worldwide. Drugs used in the prevention and treatment of atherothrombosis have pharmacokinetic limitations and adverse effects such as hemorrhagic conditions, highlighting the importance of developing more effective antiplatelet agents. Methods: In this work, we synthesized N,N'-disubstituted ureas 3a-3j and evaluated their antiplatelet profiles through in vitro, ex vivo, and in silico studies. Results: The synthesized derivatives exhibited a selective inhibitory profile against platelet aggregation induced by arachidonic acid (AA) in vitro, without significantly affecting other aspects of primary hemostasis and blood coagulation. The compounds that showed inhibition greater than 85% were submitted to the analysis of their potency by calculating the concentration required to inhibit 50% of platelet aggregation induced by AA (IC50). Urea derivative 3a was the most potent with IC50 of 1.45 μM. Interestingly, this derivative inhibited more than 90% of platelet aggregation induced by AA ex vivo, with a similar effect to acetylsalicylic acid. In the hemolysis assay, most of the urea derivatives presented values below 10% suggesting good hemocompatibility. Additionally, the compounds tested at 100 μM also showed no cytotoxic effects in HepG2 and Vero cells. The in silico results suggested that compound 3a may bind to the key residue of COX-1 similar to AA and known COX-1 inhibitors, and the results are also in agreement with our SAR, which suggests that the inhibition of this enzyme is the most likely mechanism of antiplatelet activity. Conclusion: Therefore, these results demonstrated that N,N'-disubstituted ureas are promising candidates for the development of novel antiplatelet agents.

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.

Oral squamous cell carcinoma (OSCC) remains a major global health burden, and current platinum-based chemotherapeutics are constrained by systemic toxicity and acquired resistance, motivating the search for novel antitumor agents. Naphthoquinones are a privileged scaffold in anticancer drug discovery. Here, we report the synthesis of 18 1,4-naphthoquinone esters (1–18), 14 of which are novel, and their first evaluation as anticancer agents against three OSCC cell lines (SCC-4, SCC-9, and SCC-25) and primary human gingival fibroblasts. Derivative 14 emerged as the lead compound, displaying a geometric mean IC50 of 5.0 μM and a geometric mean selectivity index of 9.15, outperforming, in terms of selectivity, the chemotherapeutic standards carboplatin, lapachol, and shikonin. Mechanistically, 14 induced cell death through a combined apoptotic–autophagic pathway, evidenced by membrane blebbing, G2/M arrest, sub-G1 DNA fragmentation, caspase 3/7 activation, and LC3-puncta formation, with wortmannin-mediated rescue indicating that autophagy contributes to cell death, and without detectable induction of reactive oxygen species. This phenotype was accompanied by pronounced disorganization of the actin and tubulin cytoskeletal networks, evidenced by confocal fluorescence microscopy and reduced anisotropy of both networks. Derivative 14 induced less than 5% hemolysis at concentrations up to 1000 μM and was well tolerated in C57BL/6 mice at intraperitoneal doses up to 600 mg/kg, with no mortality or morphological alterations. In silico analyses showed no violations of Lipinski’s rule of five and a topological polar surface area within the range associated with good membrane permeability, while reverse molecular docking pointed to the DNA-binding domains of topoisomerase IIα and IIβ as plausible molecular targets, with binding modes and energies comparable to doxorubicin. Together, these findings establish 14 as a selective and well-tolerated 1,4-naphthoquinone derivative, with a proposed mechanism of action, warranting further preclinical development against OSCC.

Introduction: Chagas disease is a neglected disease caused by the protozoan Trypanosoma cruzi that affects 7 million people worldwide. The current treatment is limited due to safety and efficacy issues. Therefore, the search for new antiparasitic drugs is fundamental. The enzyme squalene synthase (SQS) is an attractive therapeutic target since it participates in the ergosterol biosynthesis pathway. Objective: In the present study, we explored the Brazilian biodiversity to search for potential inhibitors of T. cruzi SQS (TcSQS) using ligand and structure-based virtual screening strategies. Materials and Methods: A virtual screening was performed within the NUBBE database, with more than 2,200 natural products (NP) or semisynthetic derivatives from the Brazilian biodiversity. Molecular docking and ADMET predictions were then performed. Results: A set of 12 NP showed interactions with TcSQS like those observed by known inhibitors and shared literature evidence that supports the predicted activity. Conclusion: Three compounds (flavonoids) showed good ADMET properties as potential inhibitors of TcSQS.

Many students struggle to understand chemistry due to the complexity of the content and abstract concepts. Teachers’ mediation based on technological, pedagogical, content knowledge (TPACK) and the contextualization of the content with everyday life may help in this process. In this study, molecular modeling was used as a tool to help teach chemistry integrated with biology. An observational, qualitative and quantitative study was conducted with 136 high school students and 167 undergraduate students. We carried out a mini course named “Is there chemistry in food” and some of the examples approached were water, sodium chloride, sucrose, lactose, oleic acid, collagen, capsaicin receptor and others. An increase in correct answers was observed by comparing the answers after the two-hour mini-course and the correct answers before the activity, reaching 46.30% in some questions. When asked about the efficiency of the method, most of the students answered positively and detached the contributions to learning, the innovative, fun, interactive or dynamic character, the visualization of the molecules, and the practice itself. Thus, molecular modeling tools can be an interesting strategy to be explored in chemistry and biology classes, especially in high school.