Antibiotic Coordination Frameworks against Antibiotic Resistance: How to Involve Students through Experimental Practices in the Search for Solutions to Public Health Problems.

For decades, multiple varieties of antibiotics have been successfully used for therapeutic purposes. Nevertheless, antibiotic resistance is currently one of the major threats to global health. This work presents an innovative laboratory practice carried out in an inorganic medicinal chemistry course within the Degrees of Pharmacy and Biochemistry for undergraduate students. This experiment includes three classes of 2 h each. The first class consisted of the mechanochemical synthesis of an antibiotic coordination framework (ACF) using a known antibiotic (nalidixic acid) and zinc as the ligand. The prepared Zn-nalidixic acid ACF (Zn-ACF) was obtained in up to 82% yield with high purity. On the second day, the synthesized Zn-ACF was characterized by Fourier-transform infrared spectroscopy (FTIR) and powder X-ray diffraction (PXRD). Finally, during the last class, the antimicrobial activity was tested against Escherichia coli by the well diffusion method. The students verified the higher antimicrobial activity of Zn-ACF compared to nalidixic acid, proving that small changes in the chemical structure can result in great biological differences. In the end, the students presented their results in a poster format, encouraging the development of their soft skills and scientific results communication and dissemination. In the future, it is expected that such a laboratory experiment at the interface between medicinal chemistry, microbiology, analytical techniques, public health, and pharmacology will lead to the development and implementation of some service-learning practices and will serve as a model to look at for other courses and institutions.

Phytochemical Study and Antiglioblastoma Activity Assessment of Plectranthus hadiensis (Forssk.) Schweinf. ex Sprenger var. hadiensis Stems.

Glioblastoma (GB) is the most malignant form of primary astrocytoma, accounting for more than 60% of all brain tumors in adults. Nowadays, due to the development of multidrug resistance causing relapses to the current treatments and the development of severe side effects resulting in reduced survival rates, new therapeutic approaches are needed. The genus Plectranthus belongs to the Lamiaceae family and is known to be rich in abietane-type diterpenes, which possess antitumor activity. Specifically, P. hadiensis (Forssk.) Schweinf. ex Sprenger has been documented for the use against brain tumors. Therefore, the aim of this work was to perform the bioguided isolation of compounds from the acetonic extract of P. hadiensis stems and to investigate the in vitro antiglioblastoma activity of the extract and its isolated constituents. After extraction, six fractions were obtained from the acetonic extract of P. hadiensis stems. In a preliminary biological screening, the fractions V and III showed the highest antioxidant and antimicrobial activities. None of the fractions were toxic in the Artemia salina assay. We obtained different abietane-type diterpenes such as 7α-acetoxy-6ß-hydroxyroyleanone (Roy) and 6ß,7ß-dihydroxyroyleanone (DiRoy), which was also in agreement with the HPLC-DAD profile of the extract. Furthermore, the antiproliferative activity was assessed in a glioma tumor cell line panel by the Alamar blue assay. After 48 h treatment, Roy exerted strong antiproliferative/cytotoxic effects against tumor cells with low IC50 values among the different cell lines. Finally, we synthesized a new fluorescence derivative in this study to evaluate the biodistribution of Roy. The uptake of BODIPY-7α-acetoxy-6ß-hydroxyroyleanone by GB cells was associated with increased intracellular fluorescence, supporting the antiproliferative effects of Roy. In conclusion, Roy is a promising natural compound that may serve as a lead compound for further derivatization to develop future therapeutic strategies against GB.