Calcogenobiotina e 7-cloroquinolina- 1,2,3-triazoil carboxamida com potencial antiproliferativo em linhagem de carcinoma de bexiga humano

Abstract

Approximately 90% of bladder carcinomas are of the ureteral carcinoma type, which are characterized by high rates of recurrence and predisposition to progress as invasion tumor, representing one of the most costly neoplasms for health systems. Intravesical chemotherapy is a standard for the treatment of non-invasive bladder cancer. However, chemotherapy is usually aggressive and cytotoxic, which increases the death rates caused by cancer. Thus, the objective of the study was two distinct classes of drug synthesizers, calcogenobiotins and chloroquinolines, through a tumor of the human cell carcinoma (5637), as well as their cytotoxic capacity in non-tumor cells of hamster ovary (CHO-k1). Heterocyclic compounds which exhibit pharmacokinetic and pharmacodynamic properties may enhance drug affinity for a target protein by targeting the treatment. The biological and antioxidant evaluation (lipid peroxidation, free radical scavenger and thiol peroxidase) in vitro of new calcogenobiotin molecules have also been investigated as antitumor properties of a series of 7-chloroquinoline-1,2,3-triazoyl-carboxamides (QTCA), analyzing its cytotoxic activities, cell stop mechanisms, induction of cellular apoptosis, molecular docking in silico and western blotting. A prominent response was obtained for the sealing of the drug, with the advent of biotin exhibiting antioxidant and antiproliferative activity. The effective compound (5af) also did not demonstrate toxicity in vitro or in vivo studies. The cytotoxicity assay identified the dose-dependent and time-dependent cytotoxic effects after treatment with 1-(7-chloroquinolin-4-yl))- 5-methyl-N-phenyl-1H1,2,3 4-carboxylic acid (QTCA-1) and 1-(7-chloroquinolin-4-yl)-N-(4-fluorophenyl)-5- methyl-1H-1,2,3-triazoyl-4-carboxamide (QTCA-4), which is minimal in normal cells. The live/dead assay confirmed significant late cell apoptosis, while a cell cycle analysis demonstrated correction at the G0/G1 phases and test flow cytometry with Annexin VFITC/PI identified apoptotic cell death. The results in silico indicate these components through various tools to induce a cell cycle arrest and apoptosis. Western blotting confirmed the possibility of using pro and anti-apoptotic proteins. In conclusion, heterocyclic compounds are promising candidates for inducing cytotoxicity and apoptosis in human bladder cancer cells.