The nitrovinyl moiety determines the cyto- and genotoxic profiles of β-nitrostyrene derivatives: evidence from in silico and in vitro evaluation - Report - MDSpire
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The nitrovinyl moiety determines the cyto- and genotoxic profiles of β-nitrostyrene derivatives: evidence from in silico and in vitro evaluation
Clinical Report: Nitrovinyl Group Drives Cytotoxicity and Genotoxicity of β-Nitrostyrene Derivatives
Overview
This study identifies the nitrovinyl moiety as the critical structural element responsible for the cytotoxic and genotoxic effects of β-nitrostyrene derivatives. Only compounds containing this group induced cytotoxicity in tested cell lines and caused DNA double strand breaks, highlighting its key role in (geno)toxicity.
Background
β-Nitrostyrene is an industrial chemical with known antibiotic, antifungal, and anti-neoplastic properties. Despite its therapeutic potential, the structural basis for its cytotoxic and genotoxic effects remains incompletely understood. This study applied a grouping approach, combining in silico and in vitro methods, to elucidate the substructural elements responsible for these toxic effects, focusing on DNA damage endpoints such as γH2A.X phosphorylation indicative of double strand breaks.
Data Highlights
Compound No.
Name
Structural Feature
Cytotoxicity
Genotoxicity (DNA Breaks)
1
β-Nitrostyrene
Nitrovinyl moiety present
Yes
DNA double strand breaks
2
2-nitroethylbenzene
Lacks double bond in nitrovinyl moiety
No
Not specified
3
1-nitro-2-[(E)-2-nitroethenyl]benzene
Highly similar to β-nitrostyrene
Yes
DNA double strand breaks
4
Styrene
Lacks nitro group
No
Not specified
5
2-phenylethanamine
Pro-mutagenic properties
Not specified
Not specified
6
Nitrobenzene
No vinyl group
No
Not specified
7
(E)-3-phenylprop-2-enoic acid
Carboxyl replaces nitro group
No
Not specified
8
5-[(E)-2-nitroethenyl]-1,3-benzodioxole
Contains nitrovinyl moiety
Yes
Potential mutagenic activity
9
2-methoxy-5-[(E)-2-nitroethenyl]phenol
Contains nitrovinyl moiety
Yes
Non-mutagenic prediction
Key Findings
Only β-nitrostyrene derivatives containing the nitrovinyl group exhibited cytotoxic effects in L5178Y/TK± and WS1 cell lines.
The nitrovinyl moiety is responsible for inducing DNA double strand breaks, a key genotoxic event.
One compound caused DNA single strand breaks only, indicating some variation in genotoxic mechanisms.
Modification of the phenyl moiety can increase the potency of (geno)toxicity linked to the nitrovinyl group.
QSAR models and chemical descriptor analyses supported the grouping and selection of compounds for testing.
The study’s approach aids in understanding structure-activity relationships relevant to therapeutic and risk assessment contexts.
Clinical Implications
Recognition of the nitrovinyl moiety as the driver of cytotoxic and genotoxic effects in β-nitrostyrene derivatives informs risk assessment and safety profiling of these compounds. This knowledge can guide the design of safer derivatives with reduced genotoxicity or enhance the development of novel anti-cancer agents by optimizing the phenyl moiety to modulate potency.
Conclusion
The nitrovinyl group is the critical structural element mediating the cytotoxic and genotoxic effects of β-nitrostyrene derivatives. Understanding its role facilitates improved risk evaluation and therapeutic development of these compounds.
References
Doré and Viel 1975 -- In vivo anti-neoplastic properties of β-nitrostyrene
European Chemicals Agency ECHA 2017 -- Guidance on grouping of chemicals
Khoury et al. 2016 -- γH2A.X as a marker of DNA double strand breaks
Tsai et al. 2017a; Wang et al. 2017a; Panina et al. 2022 -- Studies on β-nitrostyrene derivatives
