title: The Benzyl Moiety in a Quinoxaline-Based Scaffold Acts as a DNA Intercalation Switch.
abstract: Quinoxaline antibiotics intercalate dsDNA and exhibit antitumor properties. However, they are difficult to synthesize and their structural complexity impedes a clear mechanistic understanding of DNA binding. Therefore design and synthesis of minimal-intercalators, using only part of the antibiotic scaffold so as to retain the key DNA-binding property, is extremely important. Reported is a unique example of a monomeric quinoxaline derivative of a 6-nitroquinoxaline-2,3-diamine scaffold which binds dsDNA by two different modes. While benzyl derivatives bound DNA in a sequential fashion, with intercalation as the second event, nonbenzyl derivatives showed only the first binding event. The benzyl intercalation switch provides important insights about molecular architecture which control specific DNA binding modes and would be useful in designing functionally important monomeric quinoxaline DNA binders and benchmarking molecular simulations.
authors.affiliation: Department of Organic and Medicinal Chemistry, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata, 700032, WB, India.
authors.forename: Tridib
authors.initials: T
authors.lastname: Mahata
authors.affiliation: Department of Organic and Medicinal Chemistry, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata, 700032, WB, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kanungo
authors.affiliation: Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VIIM, Kolkata, 700054, India.
authors.forename: Sudakshina
authors.initials: S
authors.lastname: Ganguly
authors.affiliation: Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VIIM, Kolkata, 700054, India.
authors.forename: Eswar Kalyan
authors.initials: EK
authors.lastname: Modugula
authors.affiliation: Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III SaltLake, Kolkata, 700 098, India.
authors.forename: Susobhan
authors.initials: S
authors.lastname: Choudhury
authors.affiliation: Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III SaltLake, Kolkata, 700 098, India.
authors.forename: Samir Kumar
authors.initials: SK
authors.lastname: Pal
authors.affiliation: Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VIIM, Kolkata, 700054, India. gautam@jcbose.ac.in.
authors.forename: Gautam
authors.initials: G
authors.lastname: Basu
authors.affiliation: Department of Organic and Medicinal Chemistry, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata, 700032, WB, India. sanjaydutta@iicb.res.in.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Dutta
mesh_terms: D002151:Calorimetry; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D007364:Intercalating Agents / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D011810:Quinoxalines / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D007364:Intercalating Agents; D011810:Quinoxalines; D004247:DNA
keywords: DNA; circular dichroism; fluorescence; heterocycles; intercalations