METHODS: Five Schiff base ligands and their complexes were synthesized, characterized, and screened against β-glucuronidase inhibitory activity.
RESULTS: In the series, compounds 3e, 3c, 2b, and 2c ascribed powerful inhibition ranging from (IC50 = 3.0 ± 0.7 µM) to (IC50 = 19.2 ± 0.8 µM). A precise and particular arrangement of atoms is suggested by the triclinic p-1 space group and the existence of a single molecule in an asymmetric unit, which are indispensable for the reactivity as well as the stability of the compounds. The analysis of the Hirshfeld surface provides information about the hydrogen intermolecular and π-π interactions. Based on molecular docking, binding potency increasing by complexation 3a-e compared to ligands 2a-e as well as reference Saccharic acid and uronic isofagomine inhibitor, suggesting that it may be a potent inhibitor of these receptors.
CONCLUSION: The work recognizes latent active compounds for novel β-glucoronidase inhibitors, by further support these may be harnessed for the development of potent drugs.
METHODS: MTT assay, DNA fragmentation, ELISA and cell cycle analysis were carried out.
RESULTS: Nordamnacanthal and damnacanthal at IC50 values of 1.7 μg/mL and10 μg/mL, respectively. At the molecular level, these compounds caused internucleosomal DNA cleavage producing multiple 180-200 bp fragments that are visible as a "ladder" on the agarose gel. This was due to the activation of the Mg2+/Ca2+-dependent endonuclease. The induction of apoptosis by nordamnacanthal was different from the one induced by damnacanthal, in a way that it occurs independently of ongoing transcription process. Nevertheless, in both cases, the process of dephosphorylation of protein phosphates 1 and 2A, the ongoing protein synthesis and the elevations of the cytosolic Ca2+ concentration were not needed for apoptosis to take place. Nordamnacanthal was found to have a cytotoxic effect by inducing apoptosis, while damnacanthal caused arrest at the G0/G1 phase of the cell cycle.
CONCLUSION: Damnacanthal and nordamnacanthal have anticancer properties, and could act as potential treatment for T-lymphoblastic leukemia.
METHODS: In vitro cytotoxicity of nordamnacanthal was tested using MTT, cell cycle and Annexin V/PI assays on human MCF-7 and MDA-MB231 breast cancer cells. Mice were orally fed with nordamnacanthal daily for 28 days for oral subchronic toxicity study. Then, the in vivo anti-tumor effect was evaluated on 4T1 murine cancer cells-challenged mice. Changes of tumor size and immune parameters were evaluated on the untreated and nordamnacanthal treated mice.
RESULTS: Nordamnacanthal was found to possess cytotoxic effects on MDA-MB231, MCF-7 and 4T1 cells in vitro. Moreover, based on the cell cycle and Annexin V results, nordamnacanthal managed to induce cell death in both MDA-MB231 and MCF-7 cells. Additionally, no mortality, signs of toxicity and changes of serum liver profile were observed in nordamnacanthal treated mice in the subchronic toxicity study. Furthermore, 50 mg/kg body weight of nordamncanthal successfully delayed the progression of 4T1 tumors in Balb/C mice after 28 days of treatment. Treatment with nordamnacanthal was also able to increase tumor immunity as evidenced by the immunophenotyping of the spleen and YAC-1 cytotoxicity assays.
CONCLUSION: Nordamnacanthal managed to inhibit the growth and induce cell death in MDA-MB231 and MCF-7 cell lines in vitro and cease the tumor progression of 4T1 cells in vivo. Overall, nordamnacanthal holds interesting anti-cancer properties that can be further explored.