title: Spectroscopic and structural studies on the interaction of an anticancer β-carboline alkaloid, harmine with GC and AT specific DNA oligonucleotides.
abstract: Harmine, a tricyclic β-carboline alkaloid possesses anticancer properties. Thus, its binding studies with DNA are considerably important because mechanism of action of anticancer drug involves DNA binding. On the other hand, the DNA binding study is also useful in drug designing and synthesis of new compounds with enhanced biological properties. Hence, the binding of harmine with sequence specific DNA oligonucleotides has been studied using various biophysical techniques i.e. absorption, fluorescence and molecular docking techniques. UV absorption study, Fluorescence quenching and Iodide quenching experiments revealed intercalation type of binding of harmine with short sequence specific DNA oligonucleotides. Fluorescence and absorption studies also concluded binding constants of harmine with GC rich DNA sequence in the order of 105M-1while with AT rich sequences it was in the order of 103M-1which clearly indicated that harmine showed greater intercalation with GC rich sequences as compared to AT rich sequences. From thermodynamic studies, it was concluded that harmine-DNA complex formation was spontaneous, exothermic and energetically favorable process. Molecular docking studies confirmed that harmine intercalates between the base pairs of DNA structure but energetically prefers intercalation between GC base pairs. Molecular docking studies and the calculated thermodynamic parameters, i.e. Gibbs free energy (ΔG), Enthalpy change (ΔH) and Entropy change (ΔS) indicated that H-bonds, van der Waals interactions and hydrophobic interactions play a major role in the binding of harmine to DNA oligomers.
authors: Applied Chemistry Lab, Faculty of Engineering, Dayalbagh Educational Institute, Dayalbagh, Agra, 282005, India.
authors: Shweta
authors: S
authors: Sharma
authors: Applied Chemistry Lab, Faculty of Engineering, Dayalbagh Educational Institute, Dayalbagh, Agra, 282005, India.
authors: Monika
authors: M
authors: Yadav
authors: Applied Chemistry Lab, Faculty of Engineering, Dayalbagh Educational Institute, Dayalbagh, Agra, 282005, India.
authors: Surendra P
authors: SP
authors: Gupta
authors: Applied Chemistry Lab, Faculty of Engineering, Dayalbagh Educational Institute, Dayalbagh, Agra, 282005, India.
authors: Kumud
authors: K
authors: Pandav
authors: Applied Chemistry Lab, Faculty of Engineering, Dayalbagh Educational Institute, Dayalbagh, Agra, 282005, India. Electronic address: kumar.surat@gmail.com.
authors: Surat
authors: S
authors: Kumar
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D020029:Base Pairing; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006247:Harmine / Q000737:chemistry* / Q000378:metabolism*; D007454:Iodides / Q000378:metabolism; D007700:Kinetics; D062105:Molecular Docking Simulation; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D007454:Iodides; D009841:Oligonucleotides; D006247:Harmine; D004247:DNA
keywords: Drug-DNA binding; Fluorescence; GC base specificity; Harmine; Intercalation; Molecular docking