ANTI-OXIDATIVE BURST, CYTOTOXICITY, AND ADME STUDIES OF THIOUREA COMPOUNDS

This oxidative stress is linked to number of immune related disorders like hypersensitivity, autoimmune disease and inflammation. In this context, many new compounds are being synthesized and screened for the purpose of immunomodulation. In current study, we are aiming to discover the potential of thiourea derivatives as potential immunomodulators via suppressing oxidative burst mechanism in macrophages and neutrophils. The immunomodulation studies were conducted using cell based spectrophotometric techniques. Fluorescent microscopy and Predictions using web-based tools. Results suggested that among three selected thiourea derivatives comp 3 significantly suppressed the superoxide anion with 86.94 +/- 1.2 percent inhibition. Additionally, comp 2 and 3 were significantly involved in inhibiting the myeloperoxidase dependent pathway that produce hypochlorite anion with IC50 value of 45.3 +/- 0.4 and 10.4 +/- 0.2 mu g/mL, respectively. Similarly, intracellular oxidative stress was suppressed by comp 2 and 3 detected by fluoresce microscopy. In addition, the comp 1 and 3 showed moderate inhibitory activity with 36.9 and 33.8% respectively. No any compound has shown cellular toxicity at the 25 mu g/mL tested fibroblast cell line. Physicochemical and Pharmacokinetic Predictions of comp 2 and 3 showed high blood brain barrier (BBB) permeability along with Gastrointestinal (GI) absorption. Prediction studies revealed the lethal dose (LD50) of 1700 mg/kg and 1400 mg/kg respectively. Additionally comp 3 showed activity against pancreatic carcinoma MIA PaCa 2, Colon adeno carcinoma SW620 and Non-small cell lung carcinoma NIH838. In conclusion, new compounds have potential of being immunomodulatory agent particularly comp 3 demonstrated intriguing biological potential that could be explored further for its mechanistic studies.