Ru(II)-Arene Complexes of Curcumin and Bisdesmethoxycurcumin Metabolites.

Curcuminoids and their complexes continue to attract attention in medicinal chemistry, but little attention has been given to their metabolic derivatives. Here, the first examples of (arene)Ru(II) complexes with curcuminoid metabolites, tetrahydrocurcumin (THcurcH), and tetrahydrobisdesmethoxycurcumin (THbdcurcH) were prepared and characterized. The neutral complexes [Ru(arene)(THcurc)Cl] and [Ru(arene)(THbdcurc)Cl] (arene = cymene, benzene, or hexamethylbenzene) were characterized by NMR spectroscopy and ESI mass spectrometry, and the crystal structures of the three complexes were determined by X-ray diffraction analysis. Compared to curcuminoids, these metabolites lose their conjugated double bond system responsible for their planarity, showing unique closed conformation structures. Both closed and open conformations have been analyzed and rationalized by using density functional theory (DFT). The cytotoxicity of the complexes was evaluated in vitro against human ovarian carcinoma cells (A2780 and A2780cisR), human breast adenocarcinoma cells (MCF-7 and MCF-7CR), as well as against non-tumorigenic human embryonic kidney cells (HEK293) and human breast (MCF-10A) cells and compared to the free ligands, cisplatin, and RAPTA-C. There is a correlation between cellular uptake and the cytotoxicity of the compounds, suggesting that cellular uptake and binding to nuclear DNA may be the major pathway for cytotoxicity. However, the levels of complex binding to DNA do not strictly correlate with the cytotoxic potency, indicating that other mechanisms are also involved. In addition, treatment of MCF-7 cells with [Ru(cym)(THcurc)Cl] showed a significant decrease in p62 protein levels, which is generally assumed as a noncisplatin-like mechanism of action involving autophagy. Hence, a cisplatin- and a noncisplatin-like concerted mechanism of action, involving both apoptosis and autophagy, is possible.

Osteoblastoma con presentación atípica en cuboides / Osteoblastoma with atypical presentation in cuboid bone

Resumen: Introducción: El osteoblastoma es un tumor osteoblástico benigno, agresivo y poco frecuente. Su localización más frecuente es en elementos posteriores de la columna vertebral y el sacro. La presentación en cuboides es excepcional. Caso clínico: Masculino de 50 años que inició padecimiento en 2005, con dolor y aumento de volumen en región dorsolateral del mediopié. En las radiografías se observa injerto óseo y una lesión en cuboides, radiotransparente, heterogénea, multilobulada, con bordes irregulares que sobrepasa la cortical lateral. Se realizó angiotomografía donde se observó la lesión hipervascularizada; en la gammagrafía se observó captación del tecnecio 99 y en la resonancia magnética se reporta una lesión con cambios postquirúrgicos, quística, multilobulada. Se tomó biopsia transquirúrgica con abundante tejido fibroconectivo, osteoblastos, nidos de tejido osteoide e hipervascularidad del estroma, aumento de celularidad sin atipias y escasas células gigantes multinucleadas. Se clasificó Enneking 2. Se inició tratamiento con resección y curetaje del tumor, crioterapia y colocación de injerto tricortical en el defecto óseo. Mostró buena evolución postquirúrgica. A los tres años del procedimiento quirúrgico se encuentra sin datos de actividad tumoral y asintomático. A pesar de que el osteoblastoma no se presenta de forma habitual en cuboides, debe tomarse en cuenta como diagnóstico diferencial. Conclusión: Los tumores óseos, a pesar de tener localizaciones habituales, pueden presentarse en zonas poco frecuentes y por lo tanto, el estudio completo clínico radiográfico e histopatológico en cada paciente es fundamental.

Abstract: Introduction: Osteoblastoma is a benign, aggressive and rare osteoblastic tumor. Its most common location is in later elements of the spine and sacrum. The cuboid presentation is exceptional. Case report: A 50-year-old male who began her condition in 2005, with pain and increased volume in the dorsolateral region of the middle foot. X-rays show bone grafting and a cuboid lesion, radiotransparent, heterogeneous, multilobed, with irregular edges that exceeds the lateral cortical. Angiotomography was performed where hypervascularized injury was observed; bone scan showed uptake of technetium 99, and MRI reported an injury with post-surgical, cystic and multilobed changes. Trans surgical biopsy was taken, increased atypia-free cellularity and few multinucleated giant cells were reported and Enneking 2 qualified. Treatment was initiated with resection of the tumor, cryotherapy, and placement of tricortical graft in the bone defect. He exhibited good post-surgical evolution. At three years of the surgical procedure, he`s without tumor and asymptomatic. Although osteoblastoma does not usually occur in cuboid, it should be taken into account as a differential diagnosis. Conclusion: Bone tumors, despite having common locations, can occur in rare areas and therefore the complete radiographic and histopathological clinical study in each patient is critical.