Synthesis, characterization, antimicrobial and cytotoxic activity of novel half-sandwich Ru(II) arene complexes with benzoylthiourea derivatives

Obradovic, Dragisa; Nikolić, Stefan; Milenković, Ivana; Milenković, Marina; Jovanović, Predrag; Savić, Vladimir; Roller, Alexander; Crnogorac, Marija Đorđić; Stanojković, Tatjana; Grgurić-Šipka, Sanja

doi:10.1016/j.jinorgbio.2020.111164

Cited by 25 publications

(19 citation statements)

References 39 publications

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“…11 Further, Obradovićet al reported a change in the coordination of the acylthiourea ligand from monodentate to bidentate when its complex was crystallized from its solution, although all spectroscopic parameters suggested monodentate coordination only. 12 They reasoned this phenomenon by saying that the monodentate compounds were the kinetic products, whereas the slow process of crystallization allowed the distortion of the molecule in order to adopt the right conformation for the coordination of S and N atoms to the Ru(II) center, forming the thermodynamic bidentate compound. 12 In general, acylthiourea ligands are known to adopt monodentate coordination with a variety of metal ions.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…11 Recently, Grguric-S ̌ipka and co-workers reported the change in coordination of the acylthiourea ligand from monodentate to bidentate during the process of crystallization. 12 Thus, although a rich diversity of coordination modes is available for the acylthiourea ligands in Ru(II)−arene systems, their coordination behavior is not yet fully understood. Predominantly, the investigations of such ligand systems, their coordination, and their biological behavior have been carried out using Ru(II)−p-cymene as the metal precursor; the reports on complexes having benzene as the arene unit are seldom found in the literature.…”

Section: ■ Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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

et al. 2022

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“…(I) These complexes exhibited remarkable cytotoxic action against the A549 and MDA-MB-231 cancer cell lines, which are better than most of the complexes reported in the literature. − This behavior probably resulted from the good lipophilicity of this class of complexes.…”

Section: Resultsmentioning

confidence: 89%

Ruthenium(II) Diphosphine Complexes with Mercapto Ligands That Inhibit Topoisomerase IB and Suppress Tumor Growth In Vivo

et al. 2021

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Ruthenium(II) complexes (Ru1–Ru5), with the general formula [Ru(N-S)(dppe)2]PF6, bearing two 1,2-bis(diphenylphosphino)ethane (dppe) ligands and a series of mercapto ligands (N-S), have been developed. The combination of these ligands in the complexes endowed hydrophobic species with high cytotoxic activity against five cancer cell lines. For the A549 (lung) and MDA-MB-231 (breast) cancer cell lines, the IC50 values of the complexes were 288- to 14-fold lower when compared to cisplatin. Furthermore, the complexes were selective for the A549 and MDA-MB-231 cancer cell lines compared to the MRC-5 nontumor cell line. The multitarget character of the complexes was investigated by using calf thymus DNA (CT DNA), human serum albumin, and human topoisomerase IB (hTopIB). The complexes potently inhibited hTopIB. In particular, complex [Ru(dmp)(dppe)2]PF6 (Ru3), bearing the 4,6-diamino-2-mercaptopyrimidine (dmp) ligand, effectively inhibited hTopIB by acting on both the cleavage and religation steps of the catalytic cycle of this enzyme. Molecular docking showed that the Ru1–Ru5 complexes have binding affinity by active sites on the hTopI and hTopI-DNA, mainly via π-alkyl and alkyl hydrophobic interactions, as well as through hydrogen bonds. Complex Ru3 displayed significant antitumor activity against murine melanoma in mouse xenograph models, but this complex did not damage DNA, as revealed by Ames and micronucleus tests.

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“…29 In another study have determined that the presence of the 4-methoxy group in benzoyl thiourea compounds with aniline groups reduces antibacterial activity (MIC: generally >1000 µg/ml). 30 Conversely, our compound contains a pyridine ring instead of a benzene ring. Commercially available large number of drugs with antimicrobial, and antioxidant activity in the market contain a pyridine ring.…”

Section: Characterizationmentioning

confidence: 95%

A novel nicotinoyl thiourea manganese complex: synthesis, characterization, and biological activity studies

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Görmez

et al. 2021

International Journal of Chemistry and Technology

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In this study, nicotinoyl thiourea synthesized by starting from nicotinic acid and 3,5-dimethoxy aniline according to the literature. The resulting product was reacted with Manganese (II) acetate tetrahydrate and nicotinoyl thiourea manganese complex was synthesized with a metal-ligand ratio of 1: 1. The chemical structure of newly synthesized metal complex was characterized by FTIR, HRMS, XRD, and elemental analysis. In the second part of the study, the antibacterial and antioxidant activities of the synthesized metal complex were investigated. According to the obtained results, metal complex did not show any antibacterial activity. However, metal complex exhibited strong or equipotent antioxidant properties compared to standard antioxidants in DPPH, ABTS, and Cuprac methods. For this reason, metal complex can be evaluated as an antioxidant agent in food protection and the treatment of many diseases related oxidative stress.

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Synthesis, characterization, antimicrobial and cytotoxic activity of novel half-sandwich Ru(II) arene complexes with benzoylthiourea derivatives

Cited by 25 publications

References 39 publications

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

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

Ruthenium(II) Diphosphine Complexes with Mercapto Ligands That Inhibit Topoisomerase IB and Suppress Tumor Growth In Vivo

A novel nicotinoyl thiourea manganese complex: synthesis, characterization, and biological activity studies

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