IN VITRO ANTITUMORAL ACTIVITY OF MESOIONIC SALTS ON OSTEOSARCOMA
Details
- Presentation type: MS - Master's student
- Track: 8. Drugs and/or Natural Products Therapy
- Keywords: Osteosarcoma; Mesoionics; chemotherapy; in vitro;
- 1 Instituto Nacional de Traumatologia e Ortopedia
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Abstract
INTRODUCTION AND OBJECTIVES: Osteosarcoma is the most common primary bone malignancy of childhood and adolescence. The current treatment includes cycles of preoperative chemotherapy followed by surgical resection and additional cycles of postoperative chemotherapy, but there are few options of chemotherapeutic agents, and the available ones are associated with deleterious side effects. A recent trial evaluated patients with osteosarcoma and revealed that 46.9% presented a poor response to preoperative chemotherapy. Besides, others have shown that less than 20% of patients with advanced osteosarcoma will become long-term survivors, despite treatment. Therefore, the development of new compounds with promising application in osteosarcoma is imperative. Mesoionic salts belong to a class of heterocyclic compounds with chemical structures that favor the interaction with biomolecules. The antitumor activity of these salts has already been evaluated in different tumors such as hepatocarcinoma, melanoma, and carcinosarcoma. MATERIAL AND METHODS: In this work, we analyzed the cytotoxic effects of mesoionic salts (MI-4F and MI-3,4-F) and mesoionic chloride (MIC-NO2 and MIC-F) on osteosarcoma cells in vitro by the MTT reduction assay and flow cytometry with both annexin V and propidium iodide labeling. RESULTS AND CONCLUSION: We demonstrate that MIC-F and MIC-NO2 salts significantly reduced the relative viability and proliferation of MG-63 osteosarcoma cells at 24 h and 48 h, while MI-3,4-F and MI-F salts were not able to decrease cell viability. The death pathway related to cytotoxicity was identified by flow cytometry. Our preliminary results show that MIC-NO2 and MIC-F increased the number of doubly-stained cells and confirmed cell death by apoptosis. Among the four mesoionic salts evaluated, MIC-NO2 and MIC-F had cytotoxic effects on osteosarcoma cell line indicating, therefore, they may be promising as new chemotherapeutic agents against osteosarcoma.
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Amanda Cavalcanti
Olá Juliana, obrigada pelo interesse. Realmente faltaram informações sobre os compostos. Para deixar registrado aqui: "O nome mesoiônico é dado a uma classe de compostos heterocíclicos (ciclo com heteroátomos) penta-atômicos (cinco membros), com característica planar. Esses compostos possuem regiões contendo carga positiva e negativa, associadas a um sistema aromático poliheteroatômico, que favorecem sua interação com biomoléculas. Além disso, a ausência de carga líquida na molécula facilita a sua passagem através de membranas biológicas".
Em relação a diferença entre os 4 compostos utilizados, os 4 compostos possuem em comum o núcleo mesoiônico, identificado por um quadrado azul no slide da metodologia. MIC-F e MIC-NO2 são compostos aldeído para-F-cinamaldeído quando associado a um átomo de flúor (F) e para-nitro-cinamaldeído quando associados a um grupo nitro (NO2) . O MI-4F possui um átomo de flúor (F) em posição para enquanto o MI-3,4-F possui dois átomos de flúor (F), um no carbono 3 e o outro no carbono 4, ambos derivados de aldeídos benzoicos.
Além disso, o MIC-NO2 e o MIC-F possuem dupla ligação com o anel aromático do núcleo mesoiônico (quadrado laranja no slide da metodologia). Essa dupla ligação é derivada do aldeído cinâmico e é um dos fatores que colaboram para a maior lipossolubilidade das moléculas, o que poderia explicar seu maior efeito sobre as células de OS. Também é possivel que átomo de flúor no grupo cinamaldeído intensifique o efeito do composto na função mitocondrial.