Coordination Behavior of Acylthiourea Ligands in Their Ru(II)–Benzene Complexes─Structures and Anticancer Activity

Abstract

Acylthiourea ligands have applications in both synthetic and applied chemistry. The skeleton of the ligand contains several heteroatoms which offer variable coordination modes in their complexes. Herein, we report one such erratic behavior of these types of complexes upon crystallization. Six Ru­(II)–benzene complexes (B1–B6) containing the acylthiourea ligand were synthesized and adequately characterized using analytical and spectroscopic techniques. In contrast to the spectroscopic data confirming the monodentate coordination of the ligands to the Ru­(II) ion, the bidentate version in the crystal structure of their Ru­(II)–benzene complexes was observed. To the best of our knowledge, this is the only report as of now on N,S-coordinated acylthiourea ligands forming a four-membered ring in Ru­(II)–benzene complexes, while the same ligands in the Ru­(II)–p-cymene system showed a monodentate coordination. The complexes (B1–B6) exhibited good anticancer potential in A549, overcame cisplatin resistance in cisRA549, but unfortunately exhibited toxicity toward normal human umbilical vein endothelial cell lines. An increase in chain length at the C-terminal and the conjugation at the N-terminal of the acylthiourea ligands seemed to improve the cytotoxic profile of the complexes. 5-Ethynyl-2′-deoxyuridine staining helped to visualize the interruption of DNA synthesis by the active complexes B4 and B5, which was further authenticated using flow cytometry, wherein the complexes arrested the cell cycle in the S phase. The latter also proved the apoptosis mode of cell death induced by the active complexes, and the morphological changes due to apoptosis were visualized using acridine orange/ethidium bromide staining.

Ru(II)-p-Cymene Complexes of Furoylthiourea Ligands for Anticancer Applications against Breast Cancer Cells

“…In contrast to the results obtained from spectroscopy, an unusual bidentate coordination of the furoylthiourea ligands through N, S atoms with the Ru­(II) ion was seen in complexes 1 and 3 , whereas the monodentate coordination involving only S was observed in complexes 4 and 6 . Such N, S coordination of aroylthiourea ligands with Ru­(II)-arene in the solid state has already been reported by Cunha, Parveen, Obradović, and Swaminathan et al ,− Figure illustrates the thermal ellipsoid plots for the ligands and complexes, as well as the atomic labeling schemes. Crystal data and selected bond lengths and angles for the ligands and complexes are summarized in Tables S2–S5.…”

“…On the contrary, photomicrographs of the organs treated with cisplatin showed severe inflammation and edema of the kidneys, degeneration of the distal and proximal epithelial cells, accumulation of vesicles in the cytoplasm, and damage to the alveolar sacs. From these histological images, it is evident that the administration of Ru­(II) complexes 6 and 12 in the mice models did not cause any obvious damage to the organ tissues …”

“…From these histological images, it is evident that the administration of Ru(II) complexes 6 and 12 in the mice models did not cause any obvious damage to the organ tissues. 33 ■ CONCLUSIONS Furoylthiourea ligands and their Ru(II)-p-cymene complexes (1−12) were synthesized and characterized by spectroscopic methods. Although all of the complexes (1−12) displayed a ■ EXPERIMENTAL SECTION Furoylthiourea Ligand Synthesis.…”

Unraveling the Anticancer Efficacy and Biomolecular Properties of Ru(II)-Arene Complexes of Pyrene-Based Thiosemicarbazone Ligands: A Comprehensive In Silico/In Vitro Exploration

“…To ensure the purity of the final product, the isolated precipitate was subjected to multiple washes with hexane. Finally, the purified precipitate was dried under vacuum conditions …”

Nanoprodrugs encapsulated with mesoporous silica nanoparticles for combined with photothermal therapy for the treatment and care of gastric cancer

“…The proliferation of MSNP@poly(HEMA-co-PEGMA-g-DOX/R6G) and DOX to SNU-668 cells was evaluated by the MTT analysis [49][50][51]. The cytotoxicity curves showed that both MSNP@poly(HEMA-co-PEGMA-g-DOX/R6G) and DOX alone had substantial negative impacts on the proliferation and growth of SNU-668 cells (figure 7).…”