Nickel(II) bis(isatin thiosemicarbazone) complexes induced apoptosis through mitochondrial signaling pathway and G0/G1 cell cycle arrest in IM-9 cells

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 FeCl 3 (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 (X-RD) 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 X-ray diffraction. DMol 3 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 dynamic 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 IC 50 values of 33.8 μM (IC 50 = 49.9 μM-cisplatin and 8.6 μM-doxorubicin) and 29.2 (IC 50 = 26.6 μM-cisplatin and 3.8 μM-doxorubicin), respectively.

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“…The signals of phenyl ring protons of SVS2 were displayed at 7.99-7.17 ppm. A signal at 3.72 ppm is related to the protons of methyl group [48] .…”

Section: Resultsmentioning

confidence: 99%

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

Haribabu

Garisetti

Malekshah

et al. 2022

Journal of Molecular Structure

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“…The majority of hydrazone‐tethered isatin dimers 28–30 (IC 50 : 1.84–98.7 μM, MTT assay) showed potential activity against HepG2, MCF‐7, and HCT‐116 cancer cell lines, and some of them were comparable to doxorubicin (IC 50 : 2.57–3.70 μM). [ 66–71 ] The electron‐withdrawing group at the C‐5 position was beneficial to the activity for dimers 28 , whereas halogen atoms at the same position could improve the activity for dimers 29 . For pyrrole‐containing dimers 30 , introduction of methyl into pyrrole moiety (R 2 position) was favorable to the activity and the electron‐donating group at the R 1 position favored the activity when the R 2 position was methyl.…”

Section: Anticancer Activitymentioning

confidence: 99%

Isatin dimers and their biological activities

Zhang

Liu

et al. 2020

Archiv der Pharmazie

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Dimerization is a promising strategy to develop novel drug candidates that could extend the biological spectrum, enhance the activity, overcome drug resistance, as well as improve pharmacological, pharmacokinetic, and physicochemical profiles. Isatin dimers possess a broad spectrum of biological properties and the isatin dimer indirubin has already been used in the clinic, revealing the potential of isatin dimers as putative drugs. This review covers the recent advances of isatin dimers as pharmacologically significant scaffolds and the structure–activity relationship to set up the direction for the design and development of isatin dimers with higher efficiency and lower toxicity.

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“…The complexes of Ni(II) have been studied continuously for its biological activities [68][69][70][71][72][73][74][75] and attracted the attention of researchers to develop and design such more these complexes [76]. Various Ni(II) complexes with thiosemicarbazide and semicarbazide moiety [77][78][79][80] have been reported with increased antioxidant [81], anticancer [82], antiproliferative activities [83,84], antimicrobial [85], antibacterial [86], etc.…”

Section: Biological Importance Of Semicarbazones and Thiosemicarbazonesmentioning

confidence: 99%

Biological Applications of Co(II) and Ni(II) Complexes of Semicarbazones and Thiosemicarbazones

Jain¹,

Kumar²,

Chandra³

2018

Asian J. Chem.

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Nickel(II) bis(isatin thiosemicarbazone) complexes induced apoptosis through mitochondrial signaling pathway and G0/G1 cell cycle arrest in IM-9 cells

Cited by 74 publications

References 77 publications

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

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

Isatin dimers and their biological activities

Biological Applications of Co(II) and Ni(II) Complexes of Semicarbazones and Thiosemicarbazones

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