Lomentospora prolificans is a pathogenic and multidrug-resistant fungus that can infect both immunocompetent and immunocompromised patients, with mortality rates up to 87%. The World Health Organization (WHO) included this fungal species in its first list of 19 priority fungal pathogens, which focused on fungal pathogens that can cause invasive acute and subacute systemic fungal infections. Therefore, there is a growing interest in finding new therapeutic alternatives. In this work, the synthesis of twelve α-aminophosphonates by the microwave-assisted Kabachnik–Fields reaction and twelve α-aminophosphonic acids by a monohydrolysis reaction is reported. All compounds were evaluated by the agar diffusion method as a preliminary screening in comparison with voriconazole, showing inhibition halos for compounds 7, 11, 13, 22 and 27. The five active compounds in the preliminary tests were evaluated against five strains of L. prolificans following protocol M38-A2 from CLSI. The results showed that these compounds exhibit antifungal activity in the concentration range of 900->900 μg/mL. Cytotoxicity against healthy COS-7 cells was also evaluated by the MTT assay, and it was shown that compound 22 was the least cytotoxic, with a viability of 67.91%, comparable to the viability exhibited by voriconazole (68.55%). Docking studies showed that the possible mechanism of action of the active compounds could be through the inhibition of the enzyme lanosterol-14-alpha-demethylase in an allosteric hydrophobic cavity.

γ-amino butyric acid (GABA) is an inhibitory neurotransmitter whose deficiency has been associated with various neurological disorders. However, its low liposolubility limits its use as a supplement. Thus, multiple investigations have focused on searching for lipophilic GABA analogs that can modulate the activity of the GABA_B receptor, which could be associated with the etiology of some central nervous system disorders. The GABA analogs available on the market are Vigabatrin, Gabapentin as well as Pregabalin and Baclofen. In this work, we report on the synthesis of GABA analogs, taking the scaffold of GABA, Pregabalin, and Baclofen as a starting point. The analogs include structural features that could favor the affinity of the molecules for the GABA_B receptor, such as heterocyclic rings in the γ-position and alkyl or p-Cl-phenyl substituents (in analogy to Pregabalin and Baclofen, respectively). These analogs were synthesized by a sequence of reactions involving an N-alkylation, a 1,4-conjugated addition of dialkyl and diarylcuprates and a basic hydrolysis. Furthermore, a computational molecular docking over the GABA_B receptor was performed to evaluate the interaction of each compound in the Baclofen binding site. With this information, we evaluated our compounds as GABA_B agonists through a QSAR analysis. Finally, by means of molecular similarity analysis, and in silico ADME prediction, we support our three best compounds (8a–b, 8d) as potential GABA_B receptor agonists.

La propagación de los Agaves spp. en México es muy extensa y el país cuenta con 151 especies endémicas. Sin embargo, prácticas como la construcción, el desarrollo de fibras, la elaboración de alimentos y bebidas alcohólicas, así como la elaboración de productos ornamentales han ocasionado una considerable disminución entre las poblaciones silvestres. En este sentido, el presente trabajo tiene como objetivo realizar la caracterización morfométrica por el método de I.S.T.A de las semillas de Agave spp. colectadas en los diferentes municipios del estado de Guerrero (Agave cupreata Trel. & A. Berger y Agave angustifolia Haw.). Los resultados obtenidos se sometieron a análisis de varianza y pruebas de medias (Tukey, p ≤ 0.05), tomándose el largo, ancho, grosor de las semillas y su volumen. El sitio de muestreo que presentó el mayor número de semillas por kilogramo (233,590) fue Lamazintla. Por otra parte, las semillas de mayor longitud, anchura y grosor se encontraron en el municipio de Alpoyeca (8.6; 6.4; 0.62 mm, respectivamente). Además el análisis de pureza demostró que la muestra obtenida en Amojileca cuenta con el mayor número de semillas maduras con un promedio del 57%.