Colorectal cancer (CRC) is a disease with high incidence and mortality, constituting the fourth most common cause of death from cancer worldwide. Naphthoquinones are attractive compounds due to their biological and structural properties. In this work, 36 naphthoquinone derivatives were synthesized and their activity evaluated against HT-29 cells. Overall, high to moderate anti-proliferative activity was observed in most members of the series, with 15 compounds classified as active (1.73 < IC50 < 18.11 μM). The naphtho[2,3-b]thiophene-4,9-dione analogs showed potent cytotoxicity, 8-hydroxy-2-(thiophen-2-ylcarbonyl)naphtho[2,3-b]thiophene-4,9-dione being the compound with the highest potency and selectivity. Our results suggest that the toxicity is improved in molecules with tricyclic naphtho[2,3-b]furan-4,9-dione and naphtho[2,3-b]thiophene-4,9-dione systems 2-substituted with an electron-withdrawing group. A 3D-QSAR study of comparative molecular field analysis (CoMFA) was carried out, resulting in the generation of a reliable model (r2 = 0.99 and q2 = 0.625). This model allowed proposing five new compounds with two-fold higher theoretical anti-proliferative activity, which would be worthwhile to synthesize and evaluate. Further investigations will be needed to determine the mechanism involved in the effect of most active compounds which are potential candidates for new anticancer agents.

Quinones are a family of bioactive compounds with known antibacterial, antiviral and antiparasitic activity. The capacity of quinoid compounds to accept electrons, due to electron-attracting (or donating) substituents at the quinone moiety, modulates their redox activity upon interaction with biological systems. Nine quinone derivate including three 2-hydroxyl-1, 4-naphthoquinone; three 4,5-and three 4,9-naphthoquinone scaffolds, were synthesized and evaluated against 3D7 and Dd2 Plasmodium falciparum strains and evaluated the oxidative stress. Cell viability was determined MTTrelated colorimetric assay (EZ4u; Biomedical, Austria). Selectivity of these compounds was evaluated by comparing in vitro, of cytotoxicity in human fibroblast and antimalarial activity in Plasmodium falciparum. Peripheral blood mononuclear cells and hemoglobin release from human erythrocytes were evaluated too. Antiplasmodial activity was evaluated by fluorometry methods. In addition, oxidized membrane protein in the malaria parasite was evaluated in vitro by derivatizatión, after treatment at IC 50 values on P. falciparum Dd2 strain. Quinones showed IC 50 values in the micromole range, selectivity indexes for quinones was variable, compounds 2 and 3 showed excellent selectivity. In vitro antiplasmodial activity was showed; this result is an incentive to continue synthesis and studying the quinoid compounds.

Purpose: Naphtho[2,3-b]furan-4,9-dione (Avicequinone B), a natural naphthoquinone isolated from the mangrove tree Avicennia alba, is recognized as a valuable synthetic precursor with anti-proliferative effect. However, the molecular mechanism involved in its bioactivity has not been investigated. This study aimed to determine the selectivity of avicequinone B against cancer cells and the transcriptomic changes induced in colorectal cancer (CRC). Methods: The cytotoxic effect against adenocarcinoma-derived cells or fibroblasts was evaluated using MTT assay. In addition, CRC cells were treated with avicequinone B in different settings to evaluate colony-forming ability, cell cycle progression, apoptosis/necrosis induction, and transcriptome response by RNA-seq. Results: Avicequinone B effectively reduced the viability of breast, colorectal, and lung adenocarcinoma cells with IC50 lower than 10 μM, while fibroblasts were less affected. The induction of G2/M arrest and necrosis-like cell death were observed in avicequinone B-treated HT-29 cells. Furthermore, RNA-seq revealed 490 differentially expressed genes, highlighting the reduction of interferon stimulated genes and proliferative signaling pathways (JAK-STAT, MAPK, and PI3K-AKT), as well as the induction of ferroptosis and miR-21 expression. Conclusion: In short, these results demonstrated the therapeutic potential of avicequinone B and paved the foundation for elucidating its mechanisms in the context of CRC.

Se presenta la información requerida para la calibración de un modelo matemático del ecosistema de la Ciénaga de Tesca de Cartagena, obtenida mediante la realización de experimentos químicos. Los parámetros cinéticos de la oxidación bioquímica se obtuvieron por el “método de la DBO”, mientras que las tasas de flujo de amonio y fosfato a través de la interfase agua – sedimento fueron evaluadas por medio de la Ley de Fick y el “modelo de descomposición de la materia orgánica en sedimentos”. La constante cinética del proceso de degradación de la materia orgánica resultó ser de 0.23 día-1, así mismo se encontró que las constantes del primer y segundo estudio de la nitrificación son 0.09 y 0.44 día-1 respectivamente. Se observaron tasas de flujo de nutrientes que oscilaron entre 30 y 4300 mg m2 día-1 para el amonio y de 0.4 a 3.5 mg m2 día-1para el fosfato. Las tasas de flujo bental de nutrientes fueron varios órdenes de magnitud más altas que las reportadas para otros ecosistemas, indicando que cuantitativamente este proceso biogeoquímico aporta grandes cantidades de amonio y fosfatos al agua de la Ciénaga, afectando negativamente la calidad de agua de este ecosistema.

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