The high mortality rate of candidemia and the limited option for the treatment of Candida spp. infection have been driving the search for new molecules with antifungal property. In this context, coordination complexes of metal ions and ligands appear to be important. Therefore, this study aimed to synthesize two new copper(II) complexes with 2-thiouracil and 6-methyl-2-thiouracil ligands and to evaluate their mutagenic potential and antifungal activity against Candida. The complexes were synthesized and characterized by infrared vibrational spectroscopy, CHN elemental analysis, UV-Vis experiments and ESI-HRMS spectrometry studies. The antifungal activity was evaluated by broth microdilution against 21 clinical isolates of Candida species. The mutagenic potential was evaluated by the Ames test. The complexes were Cu(Bipy)Cl₂(thiouracil) (Complex 1) and Cu(Bipy)Cl₂(6-methylthiouracil) (Complex 2). Complex 1 showed fungicidal and fungistatic activities against all isolates. Furthermore, the Minimum Inhibitory Concentration (MIC) from 31 to 125 µg/mL and inhibition percentage of 9.9% against the biofilms of C. krusei and C. glabrata were demonstrated. At the concentrations tested, complex 1 exhibited no mutagenic potential. Complex 2 and the free ligands exhibited no antifungal activity at the concentrations evaluated. Since complex 1 presented antifungal activity against all the tested isolates and no mutagenic potential, it could be proposed as a potential new drug for anti-Candida therapy.

The objective of this study was to use the same concentrations of aluminum (Al) and manganese (Mn) detected previously in groundwater above those permitted by Brazilian law and assess their cytotoxic and genotoxic effects in hamster ovary cell lines and their mutagenic effects through the Salmonella microsome assay. Chinese hamster ovary (CHO) and CHO-XRS5 cells were treated with different concentrations of Al and Mn (0.2 to 2.0 mg/L and 0.1 to 3.0 mg/L, respectively). The Ames test was used to analyze the concentrations of Al and Mn ranging from 0.025 to 1.0 mg/L and 0.0125 to 1.5 mg/L, respectively. Both metals showed cytotoxic effects on both cell lines and two bacterial strains (TA98 and TA100). The genotoxic effects of the highest concentrations of Al and Mn in cell lines showed nuclear buds, micronuclei, and DNA damage; however, none of the concentrations showed a positive mutagenic response in the Ames test. This is one of the few studies to demonstrate the cytotoxic effects of Al and Mn through the Ames test. In addition, the metals caused genomic instability in cell lines. Therefore, this study may help hasten the review of established regulatory standards for human consumption of groundwater.

Aleurites moluccana, pertencente à família Euphorbiaceae, é natural da Indo-Malásia, mas se introduziu em diversos países e no Brasil, adaptando-se bem ao Sul e ao Sudoeste. É conhecida popularmente por diversos nomes, como: “Castanha Purgativa”,” Castenheira”, “Nogueira da Índia” e “Noz-da-Índia”. Quanto à sua morfologia, é considerada uma árvore de porte médio e contém frutos com sementes grandes de aspecto áspero e oleoso. Seu clima favorável é o tropical, no entanto, desenvolve-se também em regiões subtropicais e semiáridas, e quanto ao solo é capaz de se estabelecer em solos barrosos, arenosos, encostas e até em barrancos. A adaptação dessa planta a diversas condições é uma das explicações da sua ampla distribuição geográfica. As folhas, cascas, tronco, seiva e sementes da A. moluccana são tradicionalmente utilizados para alimentação, ornamentação e habitação. Além disso, a A. moluccana tem grande destaque na medicina popular, sendo utilizada no tratamento de úlceras, conjuntivite, inflamação, cicatrização e analgesia. Nesse sentido, essa planta tem se tornado objetivo de estudos sobre seus componentes químicos a fim de encontrar esses metabólitos secundários que possuem tais atividades farmacológicas.

Background: Skin infections caused by Staphylococcus aureus represent a major public health concern, and plant extracts, such as those from Cochlospermum regium, have emerged as promising therapeutic alternatives. Methods: This study developed carbopol-based gel formulations containing ethanolic leaf extracts of C. regium (CRG 0.5% and 1%) and evaluated their physicochemical stability, antibacterial activity against S. aureus and a methicillin-resistant wound isolate, antioxidant potential, and biocompatibility. Results: Both CRG 0.5% and 1% were physically stable and maintained antibacterial activity for up to 90 days at 8 °C, while at 25 °C only CRG 1% retained activity throughout the evaluation period. In ex vivo pig skin assays, CRG 1% reduced methicillin-resistant S. aureus contamination by 99%, outperforming the conventional topical antibacterial agent (neomycin + bacitracin), which achieved 66% inhibition. The extract also exhibited high antioxidant activity without mutagenic or hemolytic effects. Although phenolic and flavonoid contents decreased over time, CRG 1% preserved adequate levels for therapeutic application. Conclusions: These findings indicate that CRG 1% has potential as a stable, safe, and effective alternative for the treatment of topical infections, particularly those caused by methicillin-resistant S. aureus.

Three guanidine-functionalized 3,4-dihydropyrimidin-2(1H)-imine compounds (5a, 5b, 5c) were synthesized from 3,5-diaryldiene-4-piperidone and evaluated for antibacterial and antibiofilm activity against Staphylococcus aureus, CA-MRSA and HA-MRSA. The compounds showed bacteriostatic effects (MICs: 2.34-4.68 μg/mL). In vitro antibiofilm potential was demonstrated by significant reductions in biomass and metabolic activity, and structural analyses via SEM and fluorescence microscopy. Ex vivo antibiofilm activity was confirmed in porcine skin model. RT-qPCR revealed downregulation of biofilm associated virulence genes, indicating a multifactorial mechanism. Confocal microscopy showed increased levels of extracellular DNA and proteins, suggesting disruption of the biofilm matrix. Membrane interaction assays demonstrated time- and dose-dependent effects, suggesting a complementary mechanism of action. Compounds 5a and 5c exhibited synergistic and additive effects with oxacillin. The compounds were stable intracellularly, and resistance studies revealed low induction potential. Biocompatibility was confirmed by lack of mutagenicity, hemolysis, or cytotoxicity. Moreover, in vivo efficacy was demonstrated by survival of Tenebrio molitor larvae infected with S. aureus and treated. These guanidine-based compounds are promising candidates for new MRSA drug development.