Indolo[3,2- d ][1]benzazepines (paullones), indolo[3,2- d ][2]benzazepines, and indolo[2,3- d ][2]benzazepines (latonduines) are isomeric scaffolds of current medicinal interest. Herein, we prepared a small library of novel indolo[3,2- d ][2]benzazepine-derived ligands HL 1 – HL 4 and copper(II) complexes 1 – 4 . All compounds were characterized by spectroscopic methods ( 1 H and 13 C NMR, UV–vis, IR) and electrospray ionization (ESI) mass spectrometry, while complexes 2 and 3 , in addition, by X-ray crystallography. Their purity was confirmed by HPLC coupled with high-resolution ESI mass spectrometry and/or elemental analysis. The stability of compounds in aqueous solutions in the presence of DMSO was confirmed by 1 H NMR and UV–vis spectroscopy measurements. The compounds revealed high antiproliferative activity in vitro in the breast cancer cell line MDA-MB-231 and hepatocellular carcinoma cell line LM3 in the low micromolar to nanomolar concentration range. Important structure–activity relationships were deduced from the comparison of anticancer activities of HL 1 – HL 4 and 1 – 4 with those of structurally similar paullone-derived ( HL 5 – HL 7 and 5 – 7 ) and latonduine-derived scaffolds ( HL 8 – HL 11 and 8 – 11 ). The high anticancer activity of the lead drug candidate 4 was linked to reactive oxygen species and endoplasmic reticulum stress induction, which were confirmed by fluorescent microscopy and Western blot analysis.

Since the discovery of anticancer properties of a naturally occurring hexacyclic marine alkaloid Lamellarin D, the attempts have been made to prepare its synthetic analogues and elucidate the effects of each structural component on their activity profile. While F‐ring‐free, A‐ring‐free and B‐ring‐open lamellarins are known, E‐ring‐free analogues have never been investigated. In this work, we developed a facile and straightforward synthetic method toward E‐ring‐free lamellarin analogues based on the [3+2]‐cycloaddition. For the first time, we prepared several pentacyclic lamellarin analogues without E‐ring in their structure and assessed their cytotoxicity in a panel of cancer cell lines in comparison with several hexacyclic lamellarins. E‐ring‐free lamellarins were devoid of cytotoxicity due to their poor solubility in cellular environment.

P53 plays a key role in protecting the human genome from DNA-related mutations; however, it is one of the most frequently mutated genes in cancer. The P53 family members p63 and p73 were also shown to play important roles in cancer development and progression. Currently, there are various organic molecules from different structural classes of compounds that could reactivate the function of wild-type p53, degrade or inhibit mutant p53, etc. It was shown that: (1) the function of the wild-type p53 protein was dependent on the presence of Zn atoms, and (2) Zn supplementation restored the altered conformation of the mutant p53 protein. This prompted us to question whether the dependence of p53 on Zn and other metals might be used as a cancer vulnerability. This review article focuses on the role of different metals in the structure and function of p53, as well as discusses the effects of metal complexes based on Zn, Cu, Fe, Ru, Au, Ag, Pd, Pt, Ir, V, Mo, Bi and Sn on the p53 protein and p53-associated signaling.