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Acridines are considered an important class of compounds due to their wide variety of biological activities. In this work, we synthesized four acridine derivatives (1-4) and evaluated their biological activity against the Plasmodium falciparum W2 line, as well as studied the interaction with ctDNA and HSA using spectroscopic techniques and molecular docking. The acridine derivative 2 (IC 50  = 0.90 ± 0.08 μM) was more effective against P. falciparum than primaquine (IC 50  = 1.70 ± 0.10 μM) and similar to amsacrine (IC 50  = 0.80 ± 0.10 μM). In the fluorescence and UV-vis assays, it was verified that the acridine derivatives interact with ctDNA and HSA leading to a non-fluorescent supramolecular complex formation. The non-covalent binding constants ranged from 2.09 to 7.76 × 10 3  M -1 , indicating moderate interaction with ctDNA. Through experiments with KI, fluorescence contact energy transfer and competition assays were possible to characterize the main non-covalent binding mode of the acridines evaluated with ctDNA as intercalation. The binding constants obtained showed a high linear correlation with the IC 50 values against the antimalarial activity, suggesting that DNA may be the main biological target of these molecules. Finally, HSA interaction studies were performed and all evaluated compounds bind to the site II of the protein. The less active compounds (1 and 3) presented the highest affinity to HSA, indicating that the interaction with carrier protein can affect the (bio)availability of these compounds to the biological target., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The cytotoxic activity of the pimarane diterpene annonalide (1) and nine of its semisynthetic derivatives (2-10) was investigated against the human tumor cell lines HL-60 (leukemia), PC-3 (prostate adenocarcinoma), HepG2 (hepatocellular carcinoma), SF-295 (glioblastoma) and HCT-116 (colon cancer), and normal mouse fibroblast (L929) cells. The preparation of 2-10 involved derivatization of the side chain of 1 at C-13. Except for 2, all derivatives are being reported for the first time. Most of the tested compounds presented IC 50 s below 4.0 μM, being considered potential antitumor agents. The structures of all new compounds were elucidated by spectroscopic analyses including 2D NMR and HRMS. Additionally, the interaction of annonalide (1) with ctDNA was evaluated using spectroscopic techniques, and the formation of a supramolecular complex with the macromolecule was confirmed. Competition assays with fluorescent probes (Hoechst and ethidium bromide) and theoretical studies confirmed that 1 interacts preferentially via DNA intercalation with stoichiometric ratio of 1:1 (1:ctDNA). The ΔG value was calculated as -28.24 kJ mol -1 , and indicated that the interaction process occurs spontaneously. Docking studies revealed that van der Walls is the most important interaction in 1-DNA and EB-DNA complexes, and that both ligands (1 and EB) interact with the same DNA residues (DA6, DA17 and DT19)., (Copyright © 2018. Published by Elsevier B.V.)

Thirty-nine Schiff bases were synthesized by performing microwave-assisted condensation of the corresponding aldehydes and aromatic amines. Their reactive nitrogen species (RNS) scavenging activity and inhibitory effects against cancer cell growth were then subsequently investigated. Additionally, the interaction between the calf thymus DNA (ctDNA) and selected Schiff bases was evaluated using fluorescence spectroscopy, and their binding parameters were determined. The yields of the various compounds ranged from moderate to excellent (43-99%) after only a 2-min reaction. The hydroxylated Schiff bases 2, 8, 15, 16, 18, 20, 29, 32, 34, and 37 were found to be potent scavengers of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals with half-maximal scavenging concentration (SC 50 ) values lower than that of the positive control, resveratrol. The presence of hydroxyl substituents on the aromatic rings also proved essential to the cytotoxicity of the compounds. The binding constants (K b ) obtained using fluorescence spectroscopy ranged from 0.37 to 3.07×10 5 Lmol -1 , and were strongly influenced by the structure and hydroxylation degree. Schiff bases 3 and 8 showed promising cytotoxic activity, with half-maximal growth inhibitory (GI 50 ) values in the same order of magnitude as those exhibited by the reference drug, doxorubicin against various cell lines. Interestingly, these compounds also showed the highest K b , suggesting that the cytotoxic activity could be related to their interaction with the DNA of the tumor cells. The results of this study highlighted some Schiff bases as potential lead compounds for the design of new free radical scavengers and anticancer agents., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The interaction of small molecules with DNA has been quite important, since this biomolecule is currently the major target for a wide range of drugs in clinical use or advanced clinical research phase. Thus, the present work aimed to assess the interaction process between the bioactive compound 11a-N-tosyl-5-carba-pterocarpan, (LQB-223), that presents antitumor activity, with DNA, employing spectroscopic techniques, electrophoresis, viscosity and theoretical studies. Through UV-vis and molecular fluorescence spectroscopy, it was possible to infer that the preferential quenching mechanism was static, characterized by non-fluorescent supramolecular complex formation between the LQB-223 and DNA. The binding constant was 1.94∙10 3 Lmol -1 (30°C) and, according to the thermodynamic parameters, the main forces involved in the interaction process are hydrophobic. Potassium iodide assay, competition with ethidium bromide, fluorescence contact energy transfer and melting temperature profile of DNA were employed to evaluate the binding mode. Except for KI assay, all results obtained indicated minor groove as the preferential binding mode of LQB-223 to DNA. These observations were supported by ionic strength assay, viscosity and molecular dynamics and docking studies. Finally, electrophoresis analysis demonstrated that the interaction does not promote DNA fragmentation, but it leads to variation in the migration profile after increasing the ligand concentration., (Copyright © 2016 Elsevier B.V. All rights reserved.)