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Design and synthesis of enantiomeric (R)- and (S)-copper(II) and diorganotin(IV)-based antitumor agents: Their in vitro DNA binding profile, cleavage efficiency and cytotoxicity studies

Paper ID Volume ID Publish Year Pages File Format Full-Text
29762 44436 2014 10 PDF Available
Title
Design and synthesis of enantiomeric (R)- and (S)-copper(II) and diorganotin(IV)-based antitumor agents: Their in vitro DNA binding profile, cleavage efficiency and cytotoxicity studies
Abstract

•Synthesis of enantiomeric R/S-complexes 1–4 from reduced Schiff bases, L and L′.•In vitro DNA binding studies of ligands L and L′ and their complexes (R/S)-1–4.•1 (S-enantiomer) exhibited highest binding propensity towards CT DNA.•1 (S-enantiomer) displayed efficient pBR322 DNA cleavage activity.•In vitro cytotoxicity of L, L′ and complexes 1–4 by SRB was also evaluated.

New chiral reduced Schiff base ligands (R)/(S)-2-(2-hydroxy-1-phenylethylaminomethyl)phenol (L), (R)/(S)-2-(benzylamino)-2-phenylethanol (L′) and their Cu(II)/organotin(IV) complexes (1–4) were synthesized and thoroughly characterized. Preliminary in vitro DNA binding studies of (R)- and (S)-enantiomeric pairs of ligands L, L′ and complexes 1–4 were carried out employing UV–vis, fluorescence and circular dichroic techniques to evaluate their enantioselective DNA binding potential, thereby to act as antitumor chemotherapeutic drug entities. The observations demonstrated that S-enantiomer of Cu(II) complex, 1 binds more avidly to DNA in comparison to its R-enantiomeric form and organotin(IV) complex 2. This was further established by Kb and Ksv values of ligands L and L′ and (S)-/(R)-1–4 complexes, which demonstrated multifold increase in case of S-enantiomer of copper complex 1 in comparison to its R-enantiomeric form. This clearly demonstrates the chiral preference of S-enantiomer over R-enantiomer and its potency to act as a chemotherapeutic agent. Cleavage studies of 1–4 with pBR322 plasmid DNA were carried out, noticeably, S-enantiomer of complex 1 exhibited effective DNA cleavage efficiency in absence of external agents. The cytotoxicity of ligands L and L′ and (S)-/(R)-1–4 complexes was examined on a panel of 19 human tumor cell lines of different histological origins by SRB assay. In the both the cases, the S-enantiomer of complex 1 and 3 revealed remarkably good cytotoxic activity (GI50 values <10) against T24 (Urinary Bladder), DU145 (Prostate), U373MG (Astrocytoma) and HCT15, SW620 (Colon) clearly underlining the influence of enantiomeric discrimination. Interestingly, ligands L, L′ and rest of the complexes demonstrated moderate cytotoxic activity (GI50 values <40).

Graphical abstractUV–vis and CD spectra of complex 1 (R/S) upon interaction with DNA.Figure optionsDownload full-size imageDownload as PowerPoint slide

Keywords
Cu(II) and diorganotin(IV) enantiomeric complexes; Preliminary DNA binding studies; Cleavage activity; Cytotoxicity activity; SRB assay
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Design and synthesis of enantiomeric (R)- and (S)-copper(II) and diorganotin(IV)-based antitumor agents: Their in vitro DNA binding profile, cleavage efficiency and cytotoxicity studies
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 136, 5 July 2014, Pages 62–71
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
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Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
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