New frontier radioiodinated probe based on in-silico resveratrol repositioning for microtubules dynamic targeting

Abstract

Purpose As the “de novo” drug discovery faces a highly attrition rates, drug repositioning procures a heighten concern in identifying novel uses for existing medications. This study aimed to fabricate radioiodinated resveratrol as a potent microtubules interfering agent for cancer theragnosis. Methods Resveratrol was radiolabeled with radioactive iodine where the radioiodination efficiency was enlightened and the computational approaches were employed to investigate the affinity and specificity with tubulins. Furthermore, the in-vivo distribution and pharmacokinetic studies in normal and tumor induced mice were investigated. Results The maximum radioiodination yield (94.6 ± 1.66) was achieved at optimum preparation parameters stated as 100 μg/mL of oxidizing agent, 100 μg/ml of resveratrol, reaction time of 30 min and reaction pH 5. The in-silico studies showed that di-iodinated resveratrol (compound 6) exhibited the best binding score (-34.46) and interaction with the β-tubulin binding site. The in-vivo distribution in tumor models revealed a significant accumulation (4.02% ID/g) in tumor lesion at 60 min p.i. The rate of drug elimination demonstrated a mono-exponential decline of radioactivity versus time in the blood. Conclusion Radioiodinated resveratrol revealed good microtubules targeting which render it as a novel theranostic probe for cancer management.