ABSTRACT
Cancer is one of the leading causes of death worldwide and requires intense and growing research investments from the public and private sectors. This is expected to lead to the development of new medicines. A determining factor in this process is the structural understanding of molecules with potential anticancer properties. Since the major compounds used in cancer therapies fail to encompass every spectrum of this disease, there is a clear need to research new molecules for this purpose. As it follows, we have studied the class of quinolinones that seem effective for such therapy. This paper describes the structural elucidation of a novel dihydroquinoline by single-crystal X-ray diffraction and spectroscopy characterization. Topology studies were carried through Hirshfeld surfaces analysis and molecular electrostatic potential map; electronic stability was evaluated from the calculated energy of frontier molecular orbitals. Additionally, in silico studies by molecular docking indicated that this dihydroquinoline could act as an anticancer agent due to their higher binding affinity with human aldehyde dehydrogenase 1A1 (ALDH 1A1). Tests in vitro were performed for VERO (normal human skin keratinocytes), B16F10 (mouse melanoma), and MDA-MB-231 (metastatic breast adenocarcinoma), and the results certified that compound as a potential anticancer agent. A Dihydroquinoline derivative was tested against three cancer cell lines and the results attest that compound as potential anticancer agent.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Neoplasms/drug therapy , Quinolines/chemistry , Quinolines/pharmacology , Animals , Cell Line , Cell Line, Tumor , Cell Proliferation/drug effects , Chlorocebus aethiops , Crystallography, X-Ray/methods , Drug Screening Assays, Antitumor/methods , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/pharmacology , Humans , Mice , Models, Molecular , Molecular Docking Simulation/methods , Quinolones/chemistry , Quinolones/pharmacology , Structure-Activity Relationship , Vero CellsABSTRACT
BACKGROUND AND OBJECTIVES: The procedure used for screening Trypanosoma cruzi-infected blood donors by using two serological techniques has frequently led to discordant results. The TESA-blot, a confirmatory test for Chagas' disease, was applied in a survey of inconclusive sera from a Brazilian blood bank. MATERIALS AND METHODS: Four hundred and forty-eight sera, obtained from blood donors at the HRU-Fundação Hemominas, were tested by using the TESA-blot assay, a Western blotting method. Of these 448 sera, 348 had previously been determined as inconclusive for Chagas' disease owing to discordance between the indirect immunofluorescence assay (IFA) and the enzyme-linked immunosorbent assay (ELISA). RESULTS: The TESA-blot was positive for 2.87% (10/348) of the inconclusive sera, and 100% positive and negative for the sera from chagasic (n=50) and non-chagasic (n=50) donors, respectively. CONCLUSIONS: Our results clearly indicate the need to improve the diagnosis of Chagas' disease in blood banks by using new confirmatory diagnostic test(s). The TESA-blot, a new test with trypomastigote fractions of the T. cruzi Y strain, has made new approaches to the confirmation of Chagas' disease possible.