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Leishmaniasis, a zoonotic parasitic disease transmitted by infected sandflies, impacts nearly 1 million people yearly and is endemic in many countries across Asia, Africa, the Americas, and the Mediterranean; despite this, it remains a neglected disease with limited effective treatments, particularly in impoverished communities with limited access to healthcare. This study aims to repurpose approved drugs for an affordable leishmaniasis treatment. After the screening of potential drug candidates by reviewing databases and utilizing molecular docking analysis, delamanid was chosen to be incorporated into solid lipid nanoparticles (SLNPs). Both in cellulo and in vivo tests confirmed the successful payload release within macrophages and through the epidermis following topical application on murine skin. The evaluation of macrophages infected with L. infantum amastigotes showed that the encapsulated delamanid exhibited greater leishmanicidal activity compared with the free drug. The process of encapsulating delamanid in SLNPs, as demonstrated in this study, places a strong emphasis on employing minimal technology, ensuring energy efficiency, cost-effectiveness, and reproducibility. It enables consistent, low-cost production of nanomedicines, even on a small scale, offering a promising step toward more accessible and effective leishmaniasis treatments.

Antibiotic resistance is a global threat to public health, and the search for new antibacterial therapies is a current research priority. The aim of this in silico study was to test nine new fluoroquinolones previously designed with potential leishmanicidal activity against Campylobacter jejuni, Escherichia coli, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Salmonella typhi, all of which are considered by the World Health Organization to resistant pathogens of global concern, through molecular docking and molecular dynamics (MD) simulations using wild-type (WT) and mutant-type (MT) DNA gyrases as biological targets. Our results showed that compound 9FQ had the best binding energy with the active site of E. coli in both molecular docking and molecular dynamics simulations. Compound 9FQ interacted with residues of quinolone resistance-determining region (QRDR) in GyrA and GyrB chains, which are important to enzyme activity and through which it could block DNA replication. In addition to compound 9FQ, compound 1FQ also showed a good affinity for DNA gyrase. Thus, these newly designed molecules could have antibacterial activity against Gram-negative microorganisms. These findings represent a promising starting point for further investigation through in vitro assays, which can validate the hypothesis and potentially facilitate the development of novel antibiotic drugs.

The work seeks to identify molecules with inhibitory activity against the DNA gyrase of Gram-negative microorganisms resistant to fluoroquinolones. Previously designed compounds were used to study antimicrobial potential in silico. Molecular docking was performed with nine new ciprofloxacin analog molecules, optimized through the PM6/ZDO theory level, in GyrA wild type (WT) and mutant type (MT) of C. jejuni, E. coli (6RKU PDB ID), N. gonorrhoeae, P. aeruginosa, S. enteritidis, and S. typhi. The molecule with the highest affinity for GyrA was selected based on its binding free energy and inhibition constant. In addition, a retrospective docking was carried out, to guarantee the correct affinity of the ligand to the receptor at the defined binding site. The results show a molecule with greater affinity for GyrA in five microorganisms, showing a binding free energy of less than −7.0 kcal/mol, suggesting a good antibacterial activity in silico.

This work focuses on the search and development of drugs that may become new alternatives to the commercial drugs currently available for treatment of leishmaniasis. We have designed and synthesized 12 derivatives of bis(spiropyrazolone)cyclopropanes. We then characterized their potential application in therapeutic use. For this, the in vitro biological activities against three eukaryotic models—S. cerevisiae, five cancer cell lines, and the parasite L. mexicana—were evaluated. In addition, cytotoxicity against non-cancerous mammalian cells has been evaluated and other properties of interest have been characterized, such as genotoxicity, antioxidant properties and, in silico predictive adsorption, distribution, metabolism, and excretion (ADME). The results that we present here represent a first screening, indicating two derivatives of bis(spiropyrazolone)cyclopropanes as good candidates for the treatment of leishmaniasis. They have good specificity against parasites with respect to mammalian cells.

Excipients represent the complement of the active principle in any pharmaceutical form. Their function is to provide stability, protection, and to ensure absorption of the drug and acceptability in patients. Cellulose is a conventional excipient in many pharmaceutical solid dosage products. Most of the sources used to extract microcrystalline cellulose come from cotton or wood, which are expensive and in high demand from other industries. As plants are considered the main source of excipient production, we have taken advantage of the biodiversity of Ecuador to evaluate microcrystalline cellulose extracted from borojó (Alibertia patinoi), a native plant, as an excipient for solid dosage formulations. The method of choice for tablet manufacturing was direct compression since it is a conventional fabrication method in the pharmaceutical industry. First, we performed scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) in order to compare the structure and characteristics of the extracted cellulose with two reference commercial cellulose materials. Second, we performed quality tests to evaluate the use of the isolate as an excipient including fluidity, hardness, friability, and disintegration. Compared with commercial and microcrystalline cellulose, the extracted cellulose from the native plant showed comparable characteristics and is consequently a potential excipient that could be used in the pharmaceutical industry. Last, we performed a dissolution test in which we concluded that all tablets have a short release time of active principle.