Molecular docking, QSAR properties and DNA/BSA binding, anti-proliferative studies of 6-methoxy benzothiozole imine base and its metal complexes

Abstract

The molecular and QSAR (Quantitative Structure–Activity Relationship) properties of title compound 2-((6-Methoxybenzo[d]thiazol-2-ylimino)methyl)-6-ethoxyphenol (HL) were evaluated employing HyperChem 7.5 tools. The interaction of the 1a–1e complexes of HL with calf thymus DNA (CT-DNA) was investigated by absorption titrations, Fluorescence quenching and viscosity measurements. The experimental data suggest that these complexes bind to CT-DNA through an intercalative mode, wherein DNA-binding affinity of 1e is found to be greater compared to other complexes. The tryptophan emission-quenching with bovine serum albumin (BSA) experiment revealed stronger binding of 1e than other complexes in the hydrophobic region of protein. The photocleavage of plasmid pBR322 DNA investigated in the presence of the title complexes inferred conversion of supercoiled form of DNA plasmid to circular nicked form. Free-radical scavenging activity studies of HL and its metal complexes determined by their interaction with the stable free-radical DPPH have shown promising antioxidant property. Further cytotoxicity studies with HeLa and MCF-7 cell lines indicated that the compounds can efficiently inhibit the cell proliferation in a dose dependent manner. The DAPI staining assay studies revealed the higher potency of 1e to induce apoptosis.

Abbreviations
BSA	=	Bovine serum albumin protein
CT-DNA	=	Calf thymus DNA
DMSO	=	Dimethyl sulfoxide
DAPI	=	4′,-6-Diamidino-2-phenylindole dihydrochloride
ESI–MS	=	Electrospray ionization mass spectrometry
IC50	=	Half-maximal inhibitory concentration
MBTYE	=	2-((6-methoxybenzo[d]thiazol-2-ylimino) methyl)-6-ethoxyphenol
MTT	=	3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
PBS	=	Phosphate-buffered saline
Tris	=	Tris(hydroxymethyl)aminomethane

Communicated by Ramaswamy H. Sarma

Keywords:

• Antioxidant
• BSA/DNA binding
• cytotoxicity
• photocleavage
• quenching studies
• QSAR
• topoisomerase 1

Acknowledgments

The authors are thankful to the Department of Chemistry and Department of Biochemistry Osmania University, Hyderabad for providing the research facilities. We also grateful to the National Institute of Nutrition (NIN) and Center for DNA Fingerprinting and Diagnostics (CDFD) Hyderabad for providing facilities in carrying out cytotoxicity studies. We are deeply thankful for the generous funding extended from DST-FIST and DST-PURSE Projects- I & II.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We are grateful to the University Grant Commission (UGC) New Delhi, India for providing the RGNF-ST-AND-9591 Fellowship as financial assistance to one of the authors.