Background: Anticancer therapies represent the primary treatment option for a significant number of cancer patients globally; however, many of these treatments are associated with severe side effects as they target molecular structures present in both cancerous and healthy cells. In a similar context, the treatment of Chagas disease, a neglected tropical illness, is hindered by the high toxicity of the currently available drugs. Researchers are increasingly focusing on the development of safer and more selective alternatives, with natural compounds being studied as potential starting points for the creation of more effective drug candidates with a favorable therapeutic index. Objectives: The aim of this study was to design simplified curcumin-derived structures that preserved or enhanced their therapeutic activity against human lung cancer cell lines and T. cruzi, while also improving bioavailability and minimizing toxicity. Methods: In this study, curcumin and two natural curcuminoids inspired the synthesis of a chalcone and a set of bis-chalcones, compound classes known for their enhanced stability compared with their natural parent derivatives. The synthetic strategy used was the acid-catalyzed aldol condensation reaction. The stability profiles, IC₅₀ values against A549 and H460 tumor cell lines, and trypanocidal activity against T. cruzi amastigotes of these derivatives were assessed. Results: The synthesized derivatives exhibited improved stability compared with the parent compounds, along with lower IC₅₀ values in both A549 and H460 tumor cell lines. Additionally, one of the new analogs showed promising trypanocidal activity against T. cruzi amastigotes. Conclusions: This study provides a potential pathway toward the development of more effective and less toxic treatments for both cancer and Chagas disease. The simplified curcumin derivatives represent a promising foundation for designing new therapeutic agents with improved bioavailability and efficacy.

In this article, we discuss the main aspects regarding the recognition of cell surface glycoconjugates and the immunomodulation of responses against the progression of certain pathologies, such as cancer and infectious diseases. In the first part, we talk about different aspects of glycoconjugates and delve deeper into the importance of N-glycans in cancer immunotherapy. Then, we describe two important lectin families that have been very well studied in the last 20 years. Examples include the sialic acid-binding immunoglobulin (Ig)-like lectins (siglecs), and galectins. Finally, we discuss a topic that needs to be better addressed in the field of glycoimmunology: the impact of oncofetal antigens on the cells of the immune system. New findings in this area are of great importance for advancement, especially in the field of oncology, since it is already known that cellular interactions mediated by carbohydrate–carbohydrate and/or carbohydrate proteins are able to modulate the progression of different types of cancer in events that compromise the functionality of the immune responses.

Histone deacetylase 6 (HDAC6) catalyses the removal of acetyl groups from the lysine residues of a series of non-histone proteins, e.g., α-tubulin, Hsp90 and cortactin. The design of selective inhibitors of HDAC6 is related with important outcomes in the oncological, immunological and neurological fields. Herein, we describe the design, synthesis and pharmacological evaluation of a series of N-acylhydrazones (NAH) designed from the trichostatin A as HDAC6 inhibitors. The use of the phenyl linker in the design of the compounds led to HDAC6 selectivity among the HDAC family. Para-substituted phenyl-hydroxamic acids presented a more potent inhibition of HDAC6 than their meta-substituted analogs. The N- and C- methylation of the NAH framework attached to para-substituted phenyl-hydroxamic unit was evaluated and the compound LASSBio-1911 was identified as a potent and selective HDAC6 inhibitor (IC₅₀ = 15 nM). In the next step, we evaluated the influence of the cap group. We found that the use of different aromatic and heteroaromatic rings did not influence the inhibition of HDAC6. Some of these compounds were able to reduce significantly cell migration, corroborating their inhibitory profile against HDAC6. On the other hand, an analysis of their antiproliferative activity against different tumor cell lines showed that they can induce cell cycle arrest or induce apoptosis through caspase 3/7 activation, with particular relevance for hepatocellular carcinoma (HepG2) cells. References Rodrigues, D. A.; Ferreira-Silva, G. A.; Ferreira, A. C.; Fernandes, R. A.; Kwee, J. K.; Sant'Anna, C. M.; Ionta, M.; Fraga, C. A. M. J. Med. Chem., 2016, 59, 655-706. Rodrigues, D. A.; Thota, S.; Fraga, C. A. M. Mini-Rev. Med. Chem., 2016, 16, 1175-1184. Pinheiro, P. S. M.; Rodrigues, D. A.; Sant'Anna, C. M. R.; Fraga, C. A. M. Int. J. Quantum Chem., 2018;e25720.