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Article

Synthesis and Characterization of Bis-Triazolyl-Pyridine Derivatives as Noncanonical DNA-Interacting Compounds

1
Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy
2
Department of Pharmaceutical Sciences, University of Piemonte Orientale, Largo Donegani 2/3, 28100 Novara, Italy
3
Oncogenomic and Epigenetic Unit, IRCCS-Regina Elena National Cancer Institute, 00144 Rome, Italy
4
Molecular Cell Biology of Autophagy, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
5
Institute of Experimental Endocrinology and Oncology, National Research Council, 80131 Naples, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to the work.
Academic Editors: Manlio Palumbo and Claudia Sissi
Int. J. Mol. Sci. 2021, 22(21), 11959; https://doi.org/10.3390/ijms222111959
Received: 28 September 2021 / Revised: 31 October 2021 / Accepted: 1 November 2021 / Published: 4 November 2021
Besides the well-known double-helical conformation, DNA is capable of folding into various noncanonical arrangements, such as G-quadruplexes (G4s) and i-motifs (iMs), whose occurrence in gene promoters, replication origins, and telomeres highlights the breadth of biological processes that they might regulate. Particularly, previous studies have reported that G4 and iM structures may play different roles in controlling gene transcription. Anyway, molecular tools able to simultaneously stabilize/destabilize those structures are still needed to shed light on what happens at the biological level. Herein, a multicomponent reaction and a click chemistry functionalization were combined to generate a set of 31 bis-triazolyl-pyridine derivatives which were initially screened by circular dichroism for their ability to interact with different G4 and/or iM DNAs and to affect the thermal stability of these structures. All the compounds were then clustered through multivariate data analysis, based on such capability. The most promising compounds were subjected to a further biophysical and biological characterization, leading to the identification of two molecules simultaneously able to stabilize G4s and destabilize iMs, both in vitro and in living cells. View Full-Text
Keywords: G-quadruplex; i-motif; bis-triazolyl-pyridine derivatives; click chemistry; biophysical study; immunofluorescence microscopy G-quadruplex; i-motif; bis-triazolyl-pyridine derivatives; click chemistry; biophysical study; immunofluorescence microscopy
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MDPI and ACS Style

Di Porzio, A.; Galli, U.; Amato, J.; Zizza, P.; Iachettini, S.; Iaccarino, N.; Marzano, S.; Santoro, F.; Brancaccio, D.; Carotenuto, A.; De Tito, S.; Biroccio, A.; Pagano, B.; Tron, G.C.; Randazzo, A. Synthesis and Characterization of Bis-Triazolyl-Pyridine Derivatives as Noncanonical DNA-Interacting Compounds. Int. J. Mol. Sci. 2021, 22, 11959. https://doi.org/10.3390/ijms222111959

AMA Style

Di Porzio A, Galli U, Amato J, Zizza P, Iachettini S, Iaccarino N, Marzano S, Santoro F, Brancaccio D, Carotenuto A, De Tito S, Biroccio A, Pagano B, Tron GC, Randazzo A. Synthesis and Characterization of Bis-Triazolyl-Pyridine Derivatives as Noncanonical DNA-Interacting Compounds. International Journal of Molecular Sciences. 2021; 22(21):11959. https://doi.org/10.3390/ijms222111959

Chicago/Turabian Style

Di Porzio, Anna, Ubaldina Galli, Jussara Amato, Pasquale Zizza, Sara Iachettini, Nunzia Iaccarino, Simona Marzano, Federica Santoro, Diego Brancaccio, Alfonso Carotenuto, Stefano De Tito, Annamaria Biroccio, Bruno Pagano, Gian C. Tron, and Antonio Randazzo. 2021. "Synthesis and Characterization of Bis-Triazolyl-Pyridine Derivatives as Noncanonical DNA-Interacting Compounds" International Journal of Molecular Sciences 22, no. 21: 11959. https://doi.org/10.3390/ijms222111959

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