Benzimidazole-1,2,3-triazole hybrid molecules: synthesis and study of their interaction with G-quadruplex DNA

Singu, Padma S.; Chilakamarthi, Ushasri; Mahadik, Namita S.; Bhamidipati, Keerti; Narasimhulu, Valipenta; Mokale, Santosh N.; Nagesh, Narayana; Kumbhare, Ravindra M.

doi:10.1039/d0md00414f

Cited by 18 publications

(9 citation statements)

References 64 publications

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“…[74] Benzimidazole-1,2,3-triazole hybrid 68 has been reported as a G-quadruplex DNA groove binding molecule that shows anticancer activity on PCV3 and B16-F10 cancer cells and also induces both G 2 /M-phase arrest and apoptosis. [75]…”

Section: 23-triazole-linked Azole Hybridsmentioning

confidence: 99%

1,2,3‐Triazole hybrids as anticancer agents: A review

Alam

2021

Archiv der Pharmazie

189

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Despite the advancements in the development of anticancer agents, more effective and safer anticancer drugs still need to be developed as the current agents cause unwanted side effects and many patients have become drug resistant. 1,2,3-Triazoles, due to their remarkable biological potential, have received considerable attention in drug discovery for the development of anticancer agents. The present review article presents an overview of the recent advances in 1,2,3-triazole hybrids with anticancer potential over the last 2 years, their chemical structures, structure-activity relationships, and mechanisms of action, as well as insights into the docking studies.

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Section: 23-triazole-linked Azole Hybridsmentioning

confidence: 99%

1,2,3‐Triazole hybrids as anticancer agents: A review

Alam

2021

Archiv der Pharmazie

189

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“…Viscometry is widely applied to accurately detect the binding mode of biological macromolecules to small molecules, particularly in the field of double-stranded DNA research. Usually, when small molecules take an embedded binding mode to bind to DNA, an increase in the viscosity coefficient eventually leads to an increase in the viscosity of the solution to be measured thanks to the increase in the axial length of DNA. , On the contrary, binding by covalent bonds results in a reduction in viscosity. However, the nonembedding mode represented by the groove binding mode does not cause any significant change in solution viscosity when acting on DNA .…”

Section: Results and Discussionmentioning

confidence: 99%

Characterization of the Binding Properties of Sorafenib to c-MYC G-Quadruplexes: Evidence for Screening Potential Ligands

Zeng

et al. 2023

J. Phys. Chem. B

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Sorafenib (Sor) is a multitarget kinase inhibitor used clinically to treat hepatocellular carcinoma and renal cancer. In this study, the interaction mechanism of Sor with c-MYC Gquadruplexes (G4) was investigated at the molecular level by computer-aided means and experiments. Molecular docking results predicted the binding of Sor to the groove of G4. Molecular dynamics (MD) simulations were used to evaluate the effect of ligand binding to G4. Ultraviolet (UV), fluorescence spectroscopy, and viscosity experiments showed that the binding site was in the groove. The UV and fluorescence titration results showed that compared with traditional G4 ligands represented by compound meso-tetra (N-methyl-4-pyridyl) porphine (TmPyP4), Sor has a lower affinity for G4. Likewise, results from fluorescence resonance energy transfer (FRET) experiments suggested that Sor could have a limited ability to stabilize G4, but it was not as prominent as that of TmPyP4. Time-resolved fluorescence spectroscopy again supported the results from steady-state fluorescence spectroscopy, indicating that a static quenching mechanism mainly drove the process. Studying the interaction mechanism of Sor and c-MYC may inspire the screening of new, selective c-MYC G4 ligands and provide ideas for the design of drugs with good stability, low toxicity, and specific targeting of G4.

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“…Further, viscosity studies of the ligands with the Gquadruplex DNA indicated the mode of interaction. [49] After complexation, the relative viscosity of DNA is enhanced as the axial length of DNA increased upon the ligand's intercalation or end-stacking mode of binding with the G4 DNA. It may be noticed from Figure S4 (Supporting Information) that the viscosity of c-MYC G-quadruplex DNA solution increased upon the addition of the two ligands APN h and APN h Me 2 .…”

Section: Chemmedchemmentioning

confidence: 99%

Deciphering the Binding Insights of Novel Disubstituted Anthraquinone Derivatives with G‐Quadruplex DNA to Exhibit Selective Cancer Cell Cytotoxicity

2022

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Anthraquinone‐based compounds are well‐known as duplex DNA as well as G‐quadruplex DNA binders. Implications of various anthraquinone derivatives for specific recognition of G‐quadruplex DNA over duplex DNA is a ‘challenging’ research work that requires adequate experience with molecular design. To address this important issue, we designed and synthesized ten new 2,6‐disubstituted anthraquinone‐based derivatives with different functionalized piperazinyl side‐chains. Among these, particular compounds with certain distant groups have shown selective and significant binding affinities toward the c‐MYC and c‐KIT G‐quadruplex DNA over the duplex DNA, as noticed from various biophysical experiments. The structural difference of quadruplex and duplex DNA was utilized to probe these derivatives for the end‐stacking mode of binding with G‐quadruplex DNA. The ability of the ligands to halt DNA synthesis by stabilizing G‐quadruplex structures is one of the crucial points to further apply them for quadruplex‐mediated anti‐cancer therapeutics. Interestingly, these ligands trigger apoptosis to exhibit selective cytotoxicity toward cancer cells over normal cells. This was further evidenced by ligand‐induced cell cycle arrest as well as cellular apoptotic morphological changes. These blood‐compatible ligands provided detailed structure‐activity relationship approaches for the molecular design of anthraquinone‐based G‐quadruplex binders.

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Benzimidazole-1,2,3-triazole hybrid molecules: synthesis and study of their interaction with G-quadruplex DNA

Abstract: The benzimidazole-1,2,3-triazole hybrid 4f selectively interacted with G-quadruplex DNA over duplex DNA, inhibits cell cycle at the G2/M phase, inducing apoptosis, and may be a G-quadruplex DNA groove binder with anticancer activity.

Cited by 18 publications

References 64 publications

1,2,3‐Triazole hybrids as anticancer agents: A review

1,2,3‐Triazole hybrids as anticancer agents: A review

Characterization of the Binding Properties of Sorafenib to c-MYC G-Quadruplexes: Evidence for Screening Potential Ligands

Deciphering the Binding Insights of Novel Disubstituted Anthraquinone Derivatives with G‐Quadruplex DNA to Exhibit Selective Cancer Cell Cytotoxicity

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