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1.
Bioorg Chem ; 141: 106838, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37717414

RESUMEN

Six pyrazolopyrimidine rhodium(III) or palladium(II) complexes, [Rh(L1)(H2O)Cl3] (1), [Rh(L2)(CH3OH)Cl3] (2), [Rh(L3)(H2O)Cl3] (3), [Rh2(L4)Cl6]·CH3OH (4), [Rh(L5)(CH3CN)Cl3]·0.5CH3CN (5), and [Pd(L5)Cl2] (6), were synthesized and characterized. These complexes showed high cytotoxicity against six tested cancer cell lines. Most of the complexes showed higher cytotoxicity to T-24 cells in vitro than cisplatin. Mechanism studies indicated that complexes 5 and 6 induced G2/M phase cell cycle arrest through DNA damage, and induced apoptosis via endoplasmic reticulum stress response. In addition, complex 5 also induced cell apoptosis via mitochondrial dysfunction. Complexes 5 and 6 showed low in vivo toxicity and high tumor growth inhibitory activity in mouse tumor models. The inhibitory effect of rhodium complex 5 on tumor growth in vivo was more pronounced than that of palladium complex 6.


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Neoplasias , Rodio , Animales , Ratones , Antineoplásicos/farmacología , Antineoplásicos/metabolismo , Rodio/farmacología , Paladio/farmacología , Línea Celular , Neoplasias/tratamiento farmacológico , Apoptosis , Complejos de Coordinación/farmacología , Línea Celular Tumoral
2.
Oncol Lett ; 28(4): 468, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39119236

RESUMEN

8p11 myeloproliferative syndrome (EMS) is a rare and aggressive hematological malignancy, characterized by myeloproliferative neoplasms, and associated with eosinophilia and T- or B-cell lineage lymphoblastic lymphoma. The pathogenesis is defined by the presence of chromosomal translocations associated with the fibroblast growth factor-1 (FGFR1) gene, located in the 8p11-12.1 chromosomal locus. At present, only ~100 cases have been reported globally. At least 15 partner genes have been identified, including the most common, the zinc finger MYM-type containing 2 (ZNF198)-FGFR1 fusion gene formed by t(8;13)(p11;q12). Different fusion genes determine the clinical manifestations and prognosis of the disease. Patients with EMS with t(8;13)(p11;q12) commonly present with lymphadenopathy and T-lymphoblastic lymphoma, which usually converts to acute myeloid leukemia (AML) with the progression of the disease. The present study describes the case of an elderly female patient with EMS with t(8;13)(p11;q12), presenting with myeloid/lymphoid syndrome (myeloproliferative neoplasms and T lymphoblastic lymphoma). The patient received the CHOPE regimen combined with tyrosine kinase inhibitor (dasatin) treatment and obtained short-term complete remission. However, 6 months later, the disease progressed from EMS to AML and the patient died due to ineffective induction therapy. The present study also reviews the relevant literature about this unusual entity to enhance the understanding of EMS.

3.
J Med Chem ; 66(14): 9592-9606, 2023 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-37432720

RESUMEN

As a continuation of our endeavors in discovering metal-based drugs with cytotoxic and antimetastatic activities, herein, we reported the syntheses of 11 new rhodium(III)-picolinamide complexes and the exploration of their potential anticancer activities. These Rh(III) complexes showed high antiproliferative activity against the tested cancer cell lines in vitro. The mechanism study indicated that Rh1 ([Rh(3a)(CH3CN)Cl2]) and Rh2 ([Rh(3b)(CH3CN)Cl2]) inhibited cell proliferation by multiple modes of action via cell cycle arrest, apoptosis, and autophagy and inhibited cell metastasis via FAK-regulated integrin ß1-mediated suppression of EGFR expression. Furthermore, Rh1 and Rh2 significantly inhibited bladder cancer growth and breast cancer metastasis in a xenograft model. These rhodium(III) complexes could be developed as potential anticancer agents with antitumor growth and antimetastasis activity.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Complejos de Coordinación , Rodio , Humanos , Femenino , Rodio/farmacología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Proliferación Celular , Autofagia , Línea Celular Tumoral , Complejos de Coordinación/farmacología , Complejos de Coordinación/uso terapéutico
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