Tumor aggressiveness is usually associated with metastasis. MDA-MB 231, a triple-negative breast cancer (TNBC), is an aggressive type of breast cancer and associated with early metastasis. The Rho/ROCK pathway is a key regulator of cell motility involving cytoskeleton regulation through stabilization of actin filaments and stress fiber formation. In this study we show that Fasudil, a ROCK inhibitor, inhibited the migration of MDA-MB 231 and A549 cells, without altering the viability of these cells at the concentration of 10 μM, modified tumor cell morphology, with disorganization of stress fibers and promotes activation of the canonical-Wnt/beta-catenin pathway. Therefore, Fasudil present a promising approach to the prevention of breast cancer metastasis through a different mechanism of action from the well-known one.

Leishmaniasis represents a series of severe neglected tropical diseases caused by protozoa of the genus Leishmania and is widely distributed around the world. Here, we present the syntheses of Morita-Baylis-Hillman adducts (MBHAs) prepared from eugenol, thymol and carvacrol, and their bioevaluation against promastigotes of Leishmania amazonensis. The new MBHAs are prepared in two steps from essential oils in moderate to good yields and present IC₅₀ values in the range of 22.30–4.71 μM. Moreover, the selectivity index to the most potent compound is very high (SIrb > 84.92), far better than that of Glucantime^® (SIrb 1.39) and amphotericin B (SIrb = 22.34). Conformational analysis were carried out at the M062X//6-31+G(d,p) level of theory to corroborate a hypothesis about the nitroaromatic bioreduction mechanism.

It is reported the synthesis of 24 Morita-Baylis-Hillman adducts (3a-3l/6a-6l) using microwave irradiation at 80 ºC or conventional protocol at 0 ºC to promote the reactions between aromatic aldehydes and methyl acrylate or acrylonitrile (81-99%). It is shown that the reaction of 2-hydroxy(4-bromophenyl)methyl acrylate formation is reversible at 120 ºC.

In this study, we synthesized a new congener series of N-sulphonylhydrazones designed as candidate ROCK inhibitors using the molecular hybridization of the clinically approved drug fasudil (1) and the IKK-β inhibitor LASSBio-1524 (2). Among the synthesized compounds, the N-methylated derivative 11 (LASSBio-2065) showed the best inhibitory profile for both ROCK isoforms, with IC₅₀ values of 3.1 and 3.8 µM for ROCK1 and ROCK2, respectively. Moreover, these compounds were also active in the scratch assay performed in human breast cancer MDA-MB 231 cells and did not display toxicity in MTT and LDH assays. Molecular modelling studies provided insights into the possible binding modes of these N-sulphonylhydrazones, which present a new molecular architecture capable of being optimized and developed as therapeutically useful ROCK inhibitors.