VIRTUAL TOXICITY STUDIES OF NOVEL SPIROAZETIDIN-2-ONES TETHERED WITH FURANS

Background and aim: Spiroazetidin-2-ones and furans are commonly used as anti-bacterial, anti-fungal, anti-inflammatory, cardiovascular activities, anticancer, antiparkinson agents etc. The purpose of this study was to perform virtual toxicity studies of the synthesized compounds 1-(substitutedphenyl)-3-chloro-5,9-bis(furan-2-ylmethylidene)-1-azaspiro[3.5]nonan-2-ones (3a-3h). Materials and methods: Computational toxicology and mutagenicity profiles of these compounds were generated by using TOPKAT 6.1 (Toxicity Prediction Komputer Assisted Technology version 6.1). The molecular structure of the query compound was given as a SMILES string and a desired TOPKAT predictor was selected, then TOPKAT automatically conducts analysis of the query compound. Results: According to TOPKAT 6.1 model the compounds 3a – 3h are non-mutagenic and devoid of aerobic biodegradability. The computed Rat oral LD₅₀ values for the compounds 3a – 3h ranged from 1.1g/kg to 115.0mg/kg. These high LD₅₀ values suggest higher safety of these compounds. The computed probability of skin irritation for all compounds was found to be 1.000 and the probability for the carcinogenicity was found to be 0.950-1.000. Conclusion: By using computerized statistical methodology, more promising molecules can be identified. These studies provided us information for research to carry out an extensive study of novel spiroazetidin-2-one tethered with furan moieties for their toxicological profile.