Coumarin-hydroxamic acid derivatives 7a–k were herein designed with a dual purpose: as antiproliferative agents and fluorescent probes. The compounds were synthesized in moderate yields (30–87%) through a simple methodology, biological evaluation was carried out on prostate (PC3) and breast cancer (BT-474 and MDA-MB-231) cell lines to determine the effects on cell proliferation and gene expression. For compounds 7c, 7e, 7f, 7i and 7j the inhibition of cancer cell proliferation was similar to that found with the reference compound at a comparable concentration (10 μM), in addition, their molecular docking studies performed on histone deacetylases 1, 6 and 8 showed strong binding to the respective active sites. In most cases, antiproliferative activity was accompanied by greater levels of cyclin-dependent kinase inhibitor p21, downregulation of the p53 tumor suppressor gene, and regulation of cyclin D1 gene expression. We conclude that compounds 7c, 7e, 7f, 7i and 7j may be considered as potential anticancer agents, considering their antiproliferative properties, their effect on the regulation of the genes, as well as their capacity to dock to the active sites. The fluorescent properties of compound 7j and 7k suggest that they can provide further insight into the mechanism of action.

The antioxidant effect of the different groups in the 2,6-positions of the new 4-ethoxy-phenols were evaluated. To address our research, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and reducing power capacity, were employed to analyze the antioxidant activity. The results of the antioxidant test indicated that most of the new molecules 6a–l presented high antioxidant activity. Compound 6f had the highest activity (1.47 ± 0.39 µg/mL) when it was compared with 2,6 di-tert-butyl hydroxytoluene (BHT, 6.72 ± 0.47 µg/mL) and trolox (2.81 ± 0.31 µg/mL) as standards using DPPH assay. ABTS method confirmed that 6f was the most active antioxidant molecule. Theoretical analysis showed that phenyl group in 6f has a similar effect in the O-H energy that t-butyl in BHA, but the steric hindrance is different. In the three tests, compound 6i turned out to be the one with the least antioxidant effect; it demonstrated the main role of hydroxyl group on the topology of the species to achieve the desired antioxidant effect, which was completely lost when this group was absent.

Derivatives of 4H-pyrans and 1,6-dihydropyridines have generated considerable attention due to their interesting biological and therapeutic values. Their pharmacological activities include vasorelaxant, anticarcinogenic, antimicrobial, and antioxidant activities. Thus, the aim of the current work is to determine the relaxant effect of synthesized 4H-pyran and 1,6-dihydropyridine derivatives with potential anti-asthmatic properties on the smooth muscle airway, with a possible Ca²⁺-channel blockade as a mechanism of action due to their analogy with 1,4-dihidropyridines. 4H-pyrans and 1,6-dihydropyridines were achieved using multicomponent reactions by microwave and conventional heating. Also, test samples were evaluated ex vivo to determine their relaxant effect on isolated rat tracheal rings pre-contracted with carbachol. All compounds evaluated showed a significant relaxant effect on carbachol-induced contraction in tracheal rat rings. Compounds 4b, 4e, 7a, and 8d were the most potent from the entire series and were also more potent than theophylline, used as a positive control. In conclusion, in the current work some relaxant compounds of the airway smooth muscle with potential to be developed as anti-asthmatic drugs were obtained.

Los medicamentos, cosméticos, alimentos y las sustancias que entran en contacto directo con el cuerpo deben ser evaluadas para determinar si pueden causar efectos nocivos en humanos. Esta evaluación comienza con estudios en células en cultivo. Las sustancias tóxicas alteran el metabolismo celular y reducen la capacidad de reproducción de las células. La dosis que reduce en un 50% la población de las células se denomina dosis citotóxica 50 (Adan et al., 2016). Otro parámetro que se evalúa en las células en cultivo es la capacidad de inducir daño al ADN. Esta propiedad está directamente relacionada con la actividad mutagénica de las sustancias y por lo tanto con la posibilidad de inducir cáncer en humanos (Kirkland et al., 2019). El plomo es una sustancia probablemente carcinógena y está presente en las pinturas, baterías, tintes y barro vidriado. En este trabajo evaluamos la dosis citotóxica 50 en 2 líneas celulares: neuroblastos y fibroblastos. Nuestros resultados demostraron que los neuroblastos son más sensibles que los fibroblastos, a la exposición durante 24 horas de plomo, y explica los efectos neurotóxicos del plomo. Sin embargo, nuestros experimentos no pueden explicar la causa de esta mayor sensibilidad.