Iron complexes play a key role in the development of neurological disorders, such as Alzheimer's disease. We provide a computational protocol based on DFT for the calculation of standard reduction potentials of iron complexes relevant to Alzheimer's disease.

Background: The most important hallmark in the neuropathology of Alzheimer’s disease (AD) is the formation of amyloid-β (Aβ) fibrils due to the misfolding/aggregation of the Aβ peptide. Preventing or reverting the aggregation process has been an active area of research. Naturally occurring products are a potential source of molecules that may be able to inhibit Aβ42 peptide aggregation. Recently, we and others reported the anti-aggregating properties of curcumin and some of its derivatives in vitro, presenting an important therapeutic avenue by enhancing these properties. Objective: To computationally assess the interaction between Aβ peptide and a set of curcumin derivatives previously explored in experimental assays. Methods: The interactions of ten ligands with Aβ monomers were studied by combining molecular dynamics and molecular docking simulations. We present the in-silico evaluation of the interaction between these derivatives and the Aβ42 peptide, both in the monomeric and fibril forms. Results: The results show that a single substitution in curcumin could significantly enhance the interaction between the derivatives and the Aβ42 monomers when compared to a double substitution. In addition, the molecular docking simulations showed that the interaction between the curcumin derivatives and the Aβ42 monomers occur in a region critical for peptide aggregation. Conclusion: Results showed that a single substitution in curcumin improved the interaction of the ligands with the Aβ monomer more so than a double substitution. Our molecular docking studies thus provide important insights for further developing/validating novel curcumin-derived molecules with high therapeutic potential for AD.

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A series of new D‐ring ethisterones substituted with 1,4‐1,2,3‐triazoles were obtained in a facile manner via click chemistry reactions. The new compounds were characterized by multinuclear NMR spectroscopy, mass spectrometry, IR and unequivocally by single crystal X‐ray diffraction studies for compound 1. The cytotoxic activity of these derivatives was tested against a series of human cancer cell lines including human glioblastoma (U‐251), human prostatic adenocarcinoma (PC‐3), human colorectal adenocarcinoma (HCT‐15), human mammary adenocarcinoma (MCF‐7), human chronic myelogenous leukemia (K562), and human lung adenocarcinoma (SKLU‐1). Derivatives (3, X=Cl) and (5, X=I) showed promising cytotoxicity activities for leukemia adenocarcinoma (K562) and lung adenocarcinoma (SKLU). CI50% of K562: 11.72±0.9 μM (3) and 24.50±1.0 μM (5). CI50% of SKLU: 14.9±0.8 μM (3) and 46.0±2.8 μM (5). In addition, DNA docking simulations showed that all compounds interact with DNA through crosslink instrastrand p‐alkyl‐like interactions.

A series of benzo [d] [1,3] azoles 2-substituted with benzyl- and allyl-sulfanyl groups were synthesized, and their cytotoxic activities were in vitro evaluated against a panel of six human cancer cell lines. The results showed that compounds BTA-1 and BMZ-2 have the best inhibitory effects, compound BMZ-2 being comparable in some cases with the reference drug tamoxifen and exhibiting a low cytotoxic effect against healthy cells. In silico molecular coupling studies at the tamoxifen binding site of ERα and GPER receptors revealed affinity and the possible mode of interaction of both compounds BTA-1 and BMZ-2.