The preparation of cocrystals from active pharmaceutical ingredients (APIs) and biologically relevant coformers offers the opportunity of obtaining compounds with more desirable physicochemical and biological properties. This work focuses on theophylline–­trimesic acid, caffeine–­isophthalic acid, and caffeine–­trimesic acid cocrystals. All the cocrystals were produced via slow evaporation and were characterized using Fourier transform infrared, differential scanning calorimetry, thermogravimetric analysis, and single-crystal X-ray diffraction. Structural characterization revealed that interactions such as CO···H, N···H···O, π–π, and C–H···π between the APIs and coformers significantly contribute to crystal packing. Density functional theory studies further revealed the electronic properties of cocrystals, as well as the functional groups that enhance their solubility. Drug activity through the weak groove-binding mode was realized through docking studies of the cocrystals with the DNA structure (Protein Data Bank identifier 1ZEW). Similarly, major interactions, including hydrogen bonding and π-π bonding, were observed between cocrystals and 4HL2, a New Delhi metallo-β-lactamase-1 produced by resistant clinical strains of K. pneumoniae. Biological studies revealed cocrystals with antimicrobial properties, particularly against clinically relevant gram-negative bacterial pathogens (Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa). So, these compounds represent a novel promising group of anti-infective agents.

In the present study, we have described the synthesis and characterisation of the theophylline hydrate (Theo hydrate), cocrystal (Theo–Phen·2H2O) and hydrated sodium co-crystal of theophylline (Na–(Theo)2ClO·2H2O), where Theo = theophylline and Phen = 1,10-phenathroline.

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The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for approximately 6.8 million deaths worldwide, threatening more than 753 million individuals. People with severe coronavirus disease-2019 (COVID-19) infection often exhibit an immunosuppression condition, resulting in greater chances of developing co-infections with bacteria and fungi, including opportunistic yeasts belonging to the Saccharomyces and Candida genera. In the present work, we have reported the case of a 75-year-old woman admitted at a Brazilian university hospital with an arterial ulcer in the left foot, which was being prepared for surgical amputation. The patient presented other underlying diseases and presented positive tests for COVID-19 prior to hospitalization. She received antimicrobial treatment, but her general condition worsened quickly, leading to death by septic shock after 4 days of hospitalization. Blood samples collected on the day she died were positive for yeast-like organisms, which were later identified as Saccharomyces cerevisiae by both biochemical and molecular methods. The fungal strain exhibited low minimal inhibitory concentration values for the antifungal agents tested (amphotericin B, 5-flucytosine, caspofungin, fluconazole and voriconazole), and it was able to produce important virulence factors, such as extracellular bioactive molecules (e.g., aspartic peptidase, phospholipase, esterase, phytase, catalase, hemolysin and siderophore) and biofilm. Despite the activity against planktonic cells, the antifungals were not able to impact the mature biofilm parameters (biomass and viability). Additionally, the S. cerevisiae strain caused the death of Tenebrio molitor larvae, depending on the fungal inoculum, and larvae immunosuppression with corticosteroids increased the larvae mortality rate. In conclusion, the present study highlighted the emergence of S. cerevisiae as an opportunistic fungal pathogen in immunosuppressed patients presenting several severe comorbidities, including COVID-19 infection.

Herein, the extraction of bioactive compounds from umbu fruit peel was optimized using thermal-assisted solid–liquid extraction. In parallel, antioxidant, antimicrobial, and inhibitory effects against α-amylase of optimized extract were also evaluated. The combination of operational conditions including the temperature (32–74 °C), ethanol concentration (13–97%), and solid/liquid ratio (1:10–1:60; w/v) was employed using a rotational central composite design for optimization. The extracts were evaluated for total phenolic compounds (TPC), total flavonoid compounds (TFC) and antioxidant capacity by ABTS•+, DPPH• and FRAP assays. The bioactive profile of the optimized extract was obtained by ultra-performance liquid chromatography coupled to quadrupole/time-of-flight mass spectrometry in electrospray ionization in both negative and positive modes. The statistically evaluated results showed that the optimal operational conditions for the recovery of bioactive compounds from umbu fruit peel included 74 °C, 37% ethanol, and a solid–liquid ratio of 1:38. Under these conditions, the obtained values were 1985 mg GAE/100 g, 1364 mg RE/100 g, 122 µmol TE/g, 174 µmol/TE g and 468 µmol Fe2+/g for TPC, TFC, ABTS•+, DPPH•, and FRAP assays, respectively. In addition, the optimized extract was effective against Gram-positive and Gram-negative bacteria (MBC ranged from 0.060 to 0.24 mg GAE/mL), as well as it was effective to inhibit α-amylase (IC50 value of 0.076 mg GAE/mL). The optimized extract showed to be mainly constituted by phenolic acids and flavonoids.