Investigação das atividades angiogênica, antiangiogênica, mutagênica e antimutagênica de uma bischalcona AB7 sintética
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2018-08-20
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Universidade Federal de Goiás
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Plant biodiversity is considered the main source of secondary metabolites useful for chemical synthesis. Among the different classes of plant metabolites with therapeutic properties are chalcones. This group represents an important class of organic compounds with numerous biological activities, such as anti-inflammatory, anti-HIV, antibacterial, antifungal and anticancer. This study aimed to investigate the angiogenic, antiangiogenic, mutagenic and antimutagenic potential of bischalcone synthetic αβ7E, 4E-1- (4-chlorophenyl) -5- (2,6,6-trimethylcyclohexen-1-yl) penta-1,4-dien -3-one (CAB7β), besides its optical properties. The angiogenesis test with the chorioallantoic membrane (CAM) of embryonated chicken eggs (Gallus domesticus) with the S180 sarcoma tumor line, the Ames and micronucleus mutagenicity tests in mouse bone marrow, and the techniques spectroscopic two-photon absorption (2PA), visible ultraviolet (UV-vis) and Z-Scan, respectively. In the angiogenic test, CAB7β promoted a significant reduction (p <0.05) in the total vessels, junctions, length and caliber of the blood vessels stimulated by the S180 cells, besides reducing the presence of the inflammatory elements in the vessels of the CAMs. Another observation was that MCAs treated with CAB7β only showed significant reductions (p <0.05) in the angiogenic process compared to the negative control group used in this study. In the Ames test, CAB7β showed a protective effect on DNA against the mutagenic action of 4-nitroquinoline-1-oxide and sodium azide, and also against the action of doxorubicin in co, pre and post-treatment models using the micronucleus test. CAB7β at the doses of 12.5 and 50 μg / plate presented a moderate cytotoxic profile in TA98 strain of S. typhimurium. In the micronucleus test, its higher dose (50mg / kg p.c.) also exhibited cytotoxic activity. However, an anti-cytotoxic pertituent of this compound was observed at all doses tested in TA100 and TA-98 strains of S. typhimurium and during co, pre and post-treatment in the micronucleus test. The experimental and theoretical results of the optical properties of CAB7β demonstrated that the absorption spectrum of this compound has an intense absorption in the region of the UVA, which is associated to a transition of the type π → π * between the HOMO - LUMO orbitals, with a transfer intramolecular charge ratio of the trimethylcyclohexen-1-yl ring to the chlorophenyl ring. Thus, we conclude that the results of this study demonstrated, therefore, the versatility of CAB7β. This molecule may be a promising target in the development of new therapies against cancer, especially against sarcoma, due to the antiangiogenic potential associated with the reduction of inflammatory elements and their significant anti-mutagenic and anti-cytotoxic effects. In addition, to present potential for the development of photoprotective filters and in photodynamic therapy given their optical properties.
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PONTES, Susy Ricardo Lemes. Investigação das atividades angiogênica, antiangiogênica, mutagênica e antimutagênica de uma bischalcona AB7 sintética. 2018. 149 f. Tese (Doutorado em Biotecnologia e Biodiversidade em Rede Pró-Centro-Oeste) - Universidade Federal de Goiás, Goiânia, 2018.