3.6 Toxicity estimation
In silico toxicity estimation of the drug moieties (2-DG and 2-DG derivative) was conducted by using Toxicity Estimation Software Tool (T.E.S.T) which predicts the key toxicity parameters (Rat acute dose LD50, bioaccumulation factor, developmental toxicity and Ames mutagenicity) on the basis of the chemical structure. The fundamental principle behind such toxicological assessment is quantitative structure activity relationship (QSAR) as generated on the basis of OECD datasets. Computational assessment of these toxicity parameters also aids in predicting the probable side effects of the test compounds (Barron et al., 2012). In the present study, the tested ligands (2-deoxy-D-glucose and 1, 3, 4, 6-Tetra-O-acetyl-2-deoxy-D-glucopyranose did not show any major signs of toxicity or side effects as shown in Table 5 . In earlier studies that has been carried out in animals and humans have proved that 2-deoxy-D-glucose and 1, 3, 4, 6-Tetra-O-acetyl-2-deoxy-D-glucopyranose are safe to be administered by all routes of administration (Mohanti et al., 1996; Singh et al., 2005; Vijayaraghavan et al., 2006). Moreover, 2-DG has already been tested for its efficacy as radio-therapeutic and cytotoxic chemotherapeutic targeting pancreatic, breast, ovarian and lung cancer. However, its short half life and very low bioaccumulation factor limits the utility of 2-DG. Certain contraindications and adverse drug reactions have also been found to be associated with higher doses of 2-DG. These complications include fatigue, dizziness, nausea and hypoglycemia. However, in previous studies conducted on brain tumor patients (glioblastoma), it was observed that most of the side effects of oral administration of 2-DG (upto doses of 250 mg /kg b.w.) are transient and reversible (Singh et al., 2005). Additionally, the said contraindications can be surmounted by using 2-DG derivatives as prodrugs. Taking this into account, tetra-acetate glucopyranose derivative of 2-DG can be used as a prodrug to improve 2-DG’s pharmacokinetics, bioavailability and its drug-like properties (Pajak et al., 2020).