Synthesis, cytotoxicity and docking studies (with SARS-CoV-2) of water-soluble binuclear Ru-p-cymene complex holding indole thiosemicarbazone ligand.

A water-soluble binuclear organometallic Ru-p-cymene complex [Ru(η6-p-cymene)(η2-L)]2 (1) was prepared from (E)-2-((1H-indol-3-yl)methylene)-N-phenylhydrazine-1-carbothioamide (HL) and [RuCl2(p-cymene)]2 in methanol at room temperature under inert atmosphere. The structure of binuclear complex was analyzed by UV-Visible, FT-IR, NMR and mass spectroscopic methods. The solid-state structure of the complex was ascertained by single crystal X-ray diffraction technique. The complex exhibited pseudo-octahedral (piano-stool) geometry around Ru(II) ion. The cytotoxic property of the ligand and complex along with cisplatin was investigated against A549-lung, MCF-7-breast, HeLa-cervical, HepG-2-liver, T24-urinary bladder and EA.hy926-endothelial cancer cells, and Vero-kidney epithelial normal cells. The complex exhibited superior activity than cisplatin against A549, HeLa and T24 cancer cells with the IC50 values of 7.70, 11.2, and 5.05 µM, respectively. The complexes were cytotoxic specifically to the cancer cells. Molecular docking studies showed good binding potential of the ligand and complex with the spike protein and main protease of SARS-CoV-2, indicating the promising role of these compounds as antiviral compounds.

Synthesis, cytotoxicity and docking studies (with SARS-CoV-2) of water-soluble binuclear Ru-p-cymene complex holding indole thiosemicarbazone ligand

Graphical abstract Piano-stool water-soluble binuclear organometallic Ru-p-cymene complex was synthesized and characterized. The complex exhibited superior activity than cisplatin against A549, HeLa, HepG-2, T24 and EA.hy926 cancer cells. The compounds showed potential binding ability towards the spike protein and main protease of SARS-CoV-2. A water-soluble binuclear organometallic Ru-p-cymene complex [Ru(η6-p-cymene)(η2-L)]2 (1) was prepared from (E)-2-((1H-indol-3-yl)methylene)-N-phenylhydrazine-1-carbothioamide (HL) and [RuCl2(p-cymene)]2 in methanol at room temperature under inert atmosphere. The structure of binuclear complex was analyzed by UV-Visible, FT-IR, NMR and mass spectroscopic methods. The solid-state structure of the complex was ascertained by single crystal X-ray diffraction technique. The complex exhibited pseudo-octahedral (piano-stool) geometry around Ru(II) ion. The cytotoxic property of the ligand and complex along with cisplatin was investigated against A549-lung, MCF7-breast, HeLa-cervical, HepG-2-liver, T24-urinary bladder and EA.hy926-endothelial cancer cells, and Vero-kidney epithelial normal cells. The complex exhibited superior activity than cisplatin against A549, HeLa and T24 cancer cells with the IC50 values of 7.70, 11.2, and 5.05 µM, respectively. The complexes were cytotoxic specifically to the cancer cells. Molecular docking studies showed good binding potential of the ligand and complex with the spike protein and main protease of SARS-CoV-2, indicating the promising role of these compounds as antiviral compounds.

Design and synthesis of heterocyclic azole based bioactive compounds: Molecular structures, quantum simulation, and mechanistic studies through docking as multi-target inhibitors of SARS-CoV-2 and cytotoxicity.

Two heterocyclic azole compounds, 3-(2,3-dihydrobenzo[d]thiazol-2-yl)-4H-chromen-4-one (SVS1) and 5-(1H-indol-3-yl)-4-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (SVS2) were obtained unexpectedly from 2-aminothiophenol and 4-oxo-4H-chromene-3-carbaldehyde (for SVS1), and (E)-2-((1H-indol-3-yl)methylene)-N-methylhydrazine-1-carbothioamide in the presence of anhydrous FeCl3 (for SVS2), respectively. The compounds were well characterized by analytical and spectroscopic tools. The molecular structures of both the compounds were determined by single crystal X-ray diffraction (XRD) study. The results obtained from density functional theory (DFT) study revealed the molecular geometry and electron distribution of the compounds, which were correlated well with the three-dimensional structures obtained from the single crystal XRD. DMol3 was used to calculate quantum chemical parameters [chemical potential (µ), global hardness (η), global softness (σ), absolute electronegativity (χ) and electrophilicity index (ω)] of SVS1 and SVS2. Molecular docking study was performed to elucidate the binding ability of SVS1 and SVS2 with SARS-CoV-2 main protease and human angiotensin-converting enzyme-2 (ACE-2) molecular targets. Interestingly, the binding efficiency of the compounds with the molecular targets was comparable with that of remdesivir (SARS-CoV-2), chloroquine and hydroxychloroquine. SVS1 showed better docking energy than SVS2. The molecular docking study was complemented by molecular dynamics simulation study of SARS-CoV-2 main protease-SVS1 complex, which further exemplified the binding ability of SVS1 with the target. In addition, SVS1, SVS2 and cisplatin were assessed for their cytotoxicity against a panel of three human cancer cells such as HepG-2 (hepatic carcinoma), T24 (bladder) and EA.hy926 (endothelial), as well as Vero (kidney epithelial cells extracted from an African green monkey) normal cells using MTT assay. The results showed that SVS2 has significant cytotoxicity against HepG-2 and EA.hy926 cells with the IC50 values of 33.8 µM (IC50 = 49.9 µM-cisplatin and 8.6 µM-doxorubicin) and 29.2 (IC50 = 26.6 µM-cisplatin and 3.8 µM-doxorubicin), respectively.