Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study

Joksimović, Nenad; Petronijević, Jelena; Janković, Nenad; Baskić, Dejan; Popović, Suzana; Todorović, D. M.; Matić, Sanja; Bogdanović, Goran A.; Tot, Aleksandar; Bugarčić, Živadin D.

doi:10.1016/j.bioorg.2019.102954

Cited by 23 publications

(15 citation statements)

References 53 publications

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“…Regarding intercalation, the enhancement of DNA viscosity is associated with the DNA length, owing to the stacking of the planar ring of the molecule between DNA base pairs [20]. On the contrary, the electrostatic and groove-binding mode leads to a twisting or bending in the DNA helix, with a slight decrease in the viscosity [71,72]. A plot between relative specific viscosity (η/ηo) 1/3 versus the concentration of the complex 1/DNA ratio (r = 0.0, 0.05, 0.1, 0.15, 0.2, 0.25) is shown in Figure 6.…”

Section: Viscosity Measurementsmentioning

confidence: 99%

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Depicting the DNA Binding and Cytotoxicity Studies against Human Colorectal Cancer of Aquabis (1-Formyl-2-Naphtholato-k2O,O′) Copper(II): A Biophysical and Molecular Docking Perspective

Alolayqi¹,

Afzal²,

Alarifi³

et al. 2021

Crystals

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In this study, we attempted to examine the biological activity of the copper(II)–based small molecule aquabis (1-formyl-2-naphtholato-k2O,O′)copper(II) (1) against colon cancer. The characterization of complex 1 was established by analytical and spectral methods in accordance with the single-crystal X-ray results. A monomeric unit of complex 1 exists in an O4 (H2O) coordination environment with slightly distorted square pyramidal geometry (τ = ~0.1). The interaction of complex 1 with calf thymus DNA (ctDNA) was determined by employing various biophysical techniques, which revealed that complex 1 binds to ctDNA at the minor groove with a binding constant of 2.38 × 105 M–1. The cytotoxicity of complex 1 towards human colorectal cell line (HCT116) was evaluated by the MTT assay, which showed an IC50 value of 11.6 μM after treatment with complex 1 for 24 h. Furthermore, the apoptotic effect induced by complex 1 was validated by DNA fragmentation pattern, which clarified that apoptosis might be regulated through the mitochondrial-mediated production of reactive oxygen species (ROS) causing DNA damage pathway. Additionally, molecular docking was also carried out to confirm the recognition of complex 1 at the minor groove.

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Section: Viscosity Measurementsmentioning

confidence: 99%

“…groove-binding mode leads to a twisting or bending in the DNA helix, with a slight decrease in the viscosity [71,72]. A plot between relative specific viscosity (η/ηo) 1/3 versus the concentration of the complex 1/DNA ratio (r = 0.0, 0.05, 0.1, 0.15, 0.2, 0.25) is shown in Figure 6.…”

Section: Viscosity Measurementsmentioning

confidence: 99%

Depicting the DNA Binding and Cytotoxicity Studies against Human Colorectal Cancer of Aquabis (1-Formyl-2-Naphtholato-k2O,O′) Copper(II): A Biophysical and Molecular Docking Perspective

Alolayqi¹,

Afzal²,

Alarifi³

et al. 2021

Crystals

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“…Interestingly, some unsaturated γ-lactam substrates have been identified as p53−MDM2 [ 20 ] and STAT3 [ 21 ] inhibitors that have strong antiproliferative activity. In addition, several 2-pyrrolidone derivatives have been described as antitumor agents [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Multicomponent Synthesis of Unsaturated γ-Lactam Derivatives. Applications as Antiproliferative Agents through the Bioisosterism Approach: Carbonyl vs. Phosphoryl Group

et al. 2022

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We report efficient synthetic methodologies for the preparation of 3-amino and 3-hydroxy 3-pyrrolin-2-ones (unsaturated γ-lactams) through a multicomponent reaction of amines, aldehydes and acetylene or pyruvate derivatives. The densely substituted γ-lactam substrates show in vitro cytotoxicity, inhibiting the growth of the carcinoma human tumor cell lines RKO (human colon epithelial carcinoma), SKOV3 (human ovarian carcinoma) and A549 (carcinomic human alveolar basal epithelial cell). In view of the possibilities for the diversity of the substituents that offer a multicomponent, synthetic methodology, an extensive structure–activity profile is presented. In addition, the bioisosteric replacement of the flat ester group by a tetrahedral phosphonate or phosphine oxide moiety in γ-lactam substrates leads to increased growth inhibition activity. Cell morphology analysis and flow cytometry assays indicate that the main pathway by which our compounds induce cytotoxicity is based on the activation of the intracellular apoptotic mechanism.

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“…Interestingly, some 2-pyrrolone substrates have been recently identified as p53−MDM2 [ 16 ] and STAT3 [ 17 ] inhibitors, which results in a strong antiproliferative activity and, besides, many other 2-pyrrolone derivatives have been described as antitumoral agents [ 18 , 19 , 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

A Multicomponent Protocol for the Synthesis of Highly Functionalized γ-Lactam Derivatives and Their Applications as Antiproliferative Agents

et al. 2021

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An efficient synthetic methodology for the preparation of 3-amino 1,5-dihydro-2H-pyrrol-2-ones through a multicomponent reaction of amines, aldehydes, and pyruvate derivatives is reported. In addition, the densely substituted lactam substrates show in vitro cytotoxicity, inhibiting the growth of carcinoma human tumor cell lines HEK293 (human embryonic kidney), MCF7 (human breast adenocarcinoma), HTB81 (human prostate carcinoma), HeLa (human epithelioid cervix carcinoma), RKO (human colon epithelial carcinoma), SKOV3 (human ovarian carcinoma), and A549 (carcinomic human alveolar basal epithelial cell). Given the possibilities in the diversity of the substituents that offer the multicomponent synthetic methodology, an extensive structure-activity profile is presented. In addition, both enantiomers of phosphonate-derived γ-lactam have been synthesized and isolated and a study of the cytotoxic activity of the racemic substrate vs. its two enantiomers is also presented. Cell morphology analysis and flow cytometry assays indicate that the main pathway by which our compounds induce cytotoxicity is based on the activation of the intracellular apoptotic mechanism.

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Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study

Cited by 23 publications

References 53 publications

Depicting the DNA Binding and Cytotoxicity Studies against Human Colorectal Cancer of Aquabis (1-Formyl-2-Naphtholato-k2O,O′) Copper(II): A Biophysical and Molecular Docking Perspective

Depicting the DNA Binding and Cytotoxicity Studies against Human Colorectal Cancer of Aquabis (1-Formyl-2-Naphtholato-k2O,O′) Copper(II): A Biophysical and Molecular Docking Perspective

Multicomponent Synthesis of Unsaturated γ-Lactam Derivatives. Applications as Antiproliferative Agents through the Bioisosterism Approach: Carbonyl vs. Phosphoryl Group

A Multicomponent Protocol for the Synthesis of Highly Functionalized γ-Lactam Derivatives and Their Applications as Antiproliferative Agents

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