Latonduine-1-Amino-Hydantoin Hybrid, Triazole-Fused Latonduine Schiff Bases and Their Metal Complexes: Synthesis, X-ray and Electron Diffraction, Molecular Docking Studies and Antiproliferative Activity

Abstract

A series of latonduine derivatives, namely 11-nitro-indolo[2,3-d]benzazepine-7-(1-amino-hydantoin) (B), triazole-fused indolo[2,3-d]benzazepine-based Schiff bases HL¹ and HL² and metal complexes [M(p-cymene)(HL¹)Cl]Cl, where M = Ru (1), Os (2), and [Cu(HL²)Cl₂] (3) were synthesized and characterized by spectroscopic techniques (UV–vis, ¹H, ¹³C, ¹⁵N–¹H HSQC NMR) and ESI mass spectrometry. The molecular structures of B and HL¹ were confirmed by single-crystal X-ray diffraction, while that of 3 by electron diffraction of nanometer size crystalline sample. Molecular docking calculations of species B in the binding pocket of PIM-1 enzyme revealed that the 1-amino-hydantoin moiety is not involved in any hydrogen-bonding interactions, even though a good accommodation of the host molecule in the ATP binding pocket of the enzyme was found. The antiproliferative activity of organic compounds B, HL¹ and HL², as well as complexes 1–3 was investigated in lung adenocarcinoma A549, colon adenocarcinoma LS-174 and triple-negative breast adenocarcinoma MDA-MB-231 cells and normal human lung fibroblast cells MRC-5 by MTT assays; then, the results are discussed.

Keywords: 

antiproliferative activity;  ;