Reposicionamento e avaliação da atividade antibacteriana e de clivagem do DNA plasmidial in vitro dos não antibióticos Anlodipino e Valsartana

Abstract

Infections caused by multiresistant microrganisms have increased considerably in recent years, reaching approximately one fifth of worldwide mortality, becoming a public health problem. Another worrying factor is the resistance to antitumor drugs that lead to therapeutic failure in cancer patients. Thus, the search for more potent and selective drugs with antibacterial and antitumor action is essential, through faster and more effective alternatives, such as drug repositioning, in order to overcome these challenges and limitations. Different non-antibiotics are reported in the literature with potential antibacterial and antitumor activity, among them the antihypertensive class. Amlodipine and valsartan are non-antibiotic drugs commonly used in the medical clinic to treat high blood pressure. Thus, the aim of this study, in the first article, was to present to the scientific community a selection of studies that address the repositioning of the non-antibiotic amlodipine and its synergistic effects in the treatment of infectious diseases. The aim of the manuscript was to evaluate the antibacterial activity in vitro alone and in association with ciprofloxacin of the amlodipine and valsartan drugs, as well as to evaluate the cleavage activity of the plasmid DNA of the studied drugs, as well as their probable mechanism of action involved. In the first article, we present sixteen studies involving anlodipine repositioning as an alternative in the treatment of microbial and neoplastic infections, demonstrating significant synergistic activity when associated with ten different drugs. In the manuscript, antibacterial activity was evaluated against ten standard American Type Culture Collection (ATCC) reference bacterial strains and thirty-one multiresistant clinical isolates (MDR) from patients admitted to the University Hospital of Santa Maria, where anlodipine alone was active against all bacteria, especially against Gram-positive as the Coagulase-negative methicillin-resistant Staphylococcus (MRSCoN). Unlike with valsartan, which was active only against two strains and one isolate. When combined with ciprofloxacin, amlodipine resulted in nine synergistic isolates, whereas valsartan did not yield significant results. Also, both drugs were able to cleave the plasmid DNA under the defined conditions of pH and temperature, and in the investigation of the probable mechanism of action involved, it is suggested that both act through the hydrolytic mechanism because they were unable to inhibit the activity of cleavage in the presence of free radical scavengers. Thus, we highlight the repositioning of these drugs as an effective way to treat infections caused by multiresistant microrganisms.