Binding of dicoumarol analog with DNA and its antioxidant studies: A biophysical insight by in-vitro and in-silico approaches.

Autor: Lavanya K; Department of Chemistry, GITAM School of Science, GITAM Deemed to be University Hyderabad Campus, 502329, India., Babu PV; Department of Pharmacology, Gokaraju Rangaraju College of Pharmacy, Bachupally, Hyderabad, Telangana 500090, India., Bodapati ATS; Department of Chemistry, GITAM School of Science, GITAM Deemed to be University Hyderabad Campus, 502329, India; Chemistry Division, BS&H Department, BVRIT College of Engineering for Women, Hyderabad 500090, India., Reddy RS; Department of Chemistry, GITAM School of Science, GITAM Deemed to be University Hyderabad Campus, 502329, India; Department of Chemistry, B V Raju Institute of Technology (BVRIT), Narsapur 502313, India., Madku SR; Department of Chemistry, GITAM School of Science, GITAM Deemed to be University Hyderabad Campus, 502329, India; Department of Chemistry, St. Francis College for Women, Hyderabad 500016, India., Sahoo BK; Department of Chemistry, GITAM School of Science, GITAM Deemed to be University Hyderabad Campus, 502329, India. Electronic address: bsahoo@gitam.edu.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2023 Jul 31; Vol. 244, pp. 125301. Date of Electronic Publication: 2023 Jun 12.
DOI: 10.1016/j.ijbiomac.2023.125301
Abstrakt: DNA is the major target for a number of pharmaceutical drugs. The interaction of drug molecules with DNA plays a major role in pharmacokinetics and pharmacodynamics. Bis-coumarin derivatives have diverse biological properties. Here, we have explored the antioxidant activity of 3,3'-Carbonylbis (7-diethylamino coumarin) (CDC) using DPPH, H 2 O 2, and superoxide scavenging studies followed by its binding mode in calf thymus-DNA (CT-DNA) using several biophysical methods including molecular docking. CDC exhibited comparable antioxidant activity to standard ascorbic acid. The UV-Visible and fluorescence spectral variations indicate the CDC-DNA complex formation. The binding constant in the range of 10 4  M -1 was obtained from spectroscopic studies at room temperature. The fluorescence quenching of CDC by CT-DNA suggested a quenching constant (K SV ) of 10 3 to 10 4  M -1 order. Thermodynamic studies at 303, 308, and 318 K revealed the observed quenching as a dynamic process besides the spontaneity of the interaction with negative free energy change. Competitive binding studies with site markers like ethidium bromide, methylene blue, and Hoechst 33258 reflect CDC's groove mode of interaction. The result was complemented by DNA melting study, viscosity measurement, and KI quenching studies. The ionic strength effect was studied to interpret the electrostatic interaction and found its insignificant role in the binding. Molecular docking studies suggested the binding location of CDC within the minor groove of CT-DNA, complementing the experimental result.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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