Proceedings of Oncobiology Symposiums
Proceedings of XIV Oncobiology Symposium

INTRODUCTION AND OBJECTIVE: Cancer implies the uncontrolled or malignant growth of cells that cause innumerable diseases that occur around the world. Among these diseases, the incidence of leukemia and lymphoma was estimated at around one million new cases. Human T-cell lymphotropic virus type-1 (HTLV-1) is an etiological agent of the adult T-cell leukemia/lymphoma (ATLL) and is an aggressive malignancy. ATLL treatment is restricted, and patients with aggressive disease have poor prognoses due to the state of immunosuppression and resistance of the leukemic cells to multiple drugs. In our previous studies with mesoionic compounds containing a substituted styryl moiety, important results for in vitro cytotoxic activity in various types of tumor cells, including leukemias and in vivo antitumor effects have been observed. Human serum albumin (HSA), one of the major proteins in the human blood circulation system, takes part in many physiological functions. HSA has a remarkable capacity for reversible binding with drugs, which helps in improving their solubility, protect their oxidation in plasma and decrease toxicity. Because of these exceptional abilities, HSA is one of the key targets to predict the pharmacokinetic profile for the development of a potential therapeutic agent. Thus, in this work, we evaluated the in vitro effect of five styryl-mesoionic derivatives on C91 and MT2 cell lines infected with HTLV-1 and Jurkat cell line. The preliminary pharmacokinetic profile of these styryl-mesoionic derivatives via affinity for HSA, were also investigated by multiple spectroscopic techniques, combined with molecular docking. MATERIAL AND METHODS: Cell viability of compounds was assessed by MTT assay (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazoliobromide) after incubation with different concentrations of compounds for 24 hours. The HSA binding affinity was investigated using multiple spectroscopic techniques (fluorescence and circular dichroism) combined with molecular docking. RESULTS AND CONCLUSION: IC50 values of all compounds were in the range of 1.51-7.70 M in HTLV-1-infected and non-infected cells. The interaction between HSA and the mesoionic compounds is spontaneous and occurs via a ground-state association. The binding does not perturb both secondary and surface structure of the albumin significantly, and the main binding pocket is the site I (subdomain IIA), where Trp-214 residue can be found. Overall, all the mesoionic compounds presented good binding parameters toward serum albumin, indicating feasible biodistribution in the human bloodstream. These promising results suggest that the styryl-mesoionic derivatives may be useful in the future for chemotherapeutic treatment of leukemias/lymphomas infected with the HTLV virus.