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In vitro cytotoxicity, genotoxicity and apoptoxicity of 8-hydroxy-3,6-disulphonaphthyl azohydroxynaphthalenes using Human Lymphocytes: Experimental and theoretical profiling

Regulatory agencies require demonstration of non-genotoxicity of new chemical entities prior to their use as pharmaceuticals or additives. Consequently, the in vitro cytotoxicity, genotoxicity and apoptoxicity of five novel monoazo colourants (8-hydroxy-3,6-disulphonaphthyl azohydroxynaphthalenes, 3...

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Published: 2023
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LEADER 00000njm a2000000a 4500
001 oai:repository.ui.edu.ng:123456789/12107
042 |a dc 
720 |a Thomas, O. E.  |e author 
720 |a Adegoke, O. A.  |e author 
720 |a Mukherjee, A.  |e author 
720 |a Banerjee, R.  |e author 
260 |c 2023 
520 |a Regulatory agencies require demonstration of non-genotoxicity of new chemical entities prior to their use as pharmaceuticals or additives. Consequently, the in vitro cytotoxicity, genotoxicity and apoptoxicity of five novel monoazo colourants (8-hydroxy-3,6-disulphonaphthyl azohydroxynaphthalenes, 3a-e) on human lymphocytes were evaluated using a cell viability assay, alkaline comet assay, DNA diffusion assay, DFT calculations and molecular docking. The test concentrations of the compounds varied from 0 to 3.4 mM. Relative to negative control, the compounds at concentrations up to 0.5mM induced small dose-dependent reduction (< 20%) in viability of lymphocytes. Statistically significant changes (p<0.05) in DNA damage parameters (percent tail DNA, tail extent moment, olive tail moment) were observed at all concentrations of 3a, 3b while 3c-e showed genotoxicity at 2.8, 0.17 and 3.4 mM respectively. Compounds 3a, 3b, 3d induced apoptosis at concentrations below cytotoxic doses while 3c and 3e were non-apoptoxic at all test concentrations. DFT calculations showed the genotoxicity of 3a-e increased with electrophilicity and ionization potentials of the compounds. Molecular docking of 3a-e with apoptosis-associated proteins revealed binding affinity patterns that were consistent with observed experimental apoptoxicity. The structure-genotoxicity relationships of five novel monoazo compounds, which can be employed in the design of safer congeners, have been elucidated. 
024 8 |a 2230-7532 
024 8 |a ui_art_thomas_invitro_2023 
024 8 |a Analytical Chemistry Letters Vol 13(1), pp. 1-16 
024 8 |a https://repository.ui.edu.ng/handle/123456789/12107 
653 |a Azo compounds 
653 |a Alkaline comet assay 
653 |a DNA diffusion assay 
653 |a DFT calculation 
653 |a Molecular docking. 
245 0 0 |a In vitro cytotoxicity, genotoxicity and apoptoxicity of 8-hydroxy-3,6-disulphonaphthyl azohydroxynaphthalenes using Human Lymphocytes: Experimental and theoretical profiling