Binding affinity and in vitro cytotoxicity of harmaline targeting different motifs of nucleic acids: An ultimate drug designing approach. Issue 4 (15th December 2017)

• Record Type: Journal Article
• Authors: Bhattacharjee, Paromita; Ghosh, Tapas; Sarkar, Sarita; Pandya, Prateek; Bhadra, Kakali
• Is Part Of: Journal of molecular recognition. Volume 31:Issue 4(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-12-15
• Subjects: cell cytotoxicity -- harmaline -- molecular docking -- nucleic acid–alkaloid interaction; Molecular recognition -- Periodicals; Models, Molecular -- Periodicals; Molecular Conformation -- Periodicals; Molecular Sequence Data -- Periodicals; Molecular Structure -- Periodicals; Carrier Proteins -- Periodicals; 572.8
• DOI: 10.1002/jmr.2687
• Languages: English
• ISSNs: 0952-3499

Abstract

Abstract: The work focuses towards interaction of harmaline, with nucleic acids of different motifs by multispectroscopic and calorimetric techniques. Findings of this study suggest that binding constant varied in the order single‐stranded (ss) poly(A) > double‐stranded calf thymus (CT) DNA > double‐stranded poly(G)·poly(C) > clover leaf tRNA Phe . Prominent structural changes of ss poly(A), CT DNA, and poly(G)· poly(C) with concomitant induction of optical activity in the bound achiral alkaloid molecule was observed, while with tRNA Phe, very weak induced circular dichroism perturbation was seen. The interaction was predominantly exothermic, enthalpy driven, and entropy favored with CT DNA and poly(G)·poly(C), while it was entropy driven with poly(A) and tRNA Phe . Intercalated state of harmaline inside poly(A), CT DNA, and poly(G)·poly(C) was shown by viscometry, ferrocyanide quenching, and molecular docking. All these findings unequivocally pointed out preference of harmaline towards ss poly(A) inducing self‐structure formation. Furthermore, harmaline administration caused a significant decrease in proliferation of HeLa and HepG2 cells with GI50 of 28μM and 11.2μM, respectively. Nucleic acid fragmentation, cellular ultramorphological changes, decreased mitochondrial membrane potential, upregulation of p53 and caspase 3, generation of reactive oxygen species, and a significant increase in the G2 /M population made HepG2 more prone to apoptosis than are HeLa cells. Abstract : Studies elucidate the role of harmaline in targeting nucleic acids of different motifs by different biophysical techniques and molecular docking. Results converge to suggest that binding constant varied in the order ss poly(A) > ds CT DNA > ds poly(rG)·poly(rC) > clover leaf tRNAphe. Harmaline prefers binding with ss poly(A) inducing self‐structure formation. The alkaloid shows apoptotic induction ability on cancer cell lines.