RESUMO
Molecular and sequencing advances have led to substantial breakthroughs in the discovery of new genes and inherited mutations associated with increased risk of developing myeloid malignancies. Many of the same germline mutated genes are also drivers of malignancy in sporadic cancer. Recognition of myeloid malignancy associated with germline mutations is essential for proper therapy, disease surveillance, informing related donor selection for hematopoietic stem cell transplantation, and genetic counseling of the patient and affected family members. Some germline mutations are associated with syndromic features that precede the development of malignancy; however, penetrance may be highly variable leading to masking of the syndromic phenotype and/or inherited etiology.
Assuntos
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Genótipo , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genéticaRESUMO
Two Zn(II) nitro porphyrin derivatives bearing combinations of meso-4-nitrophenyl and meso-4-methylpyridinium moieties and their free-base precursors were synthesized through one-pot microwave process, purified and characterized. The biological activity of these nitroporphyrins was assessed under both photodynamic and non-photodynamic conditions to correlate their structure-activity relationship (SAR). Unlike, the free-base precursors, Zn(II) complexes of these nitroporphyrins displayed nearly complete inhibition in the entry of lentiviruses such as HIV-1 and SIVmac under non-photodynamic conditions. In addition, the Zn(II) complexes also exhibited a higher in vitro photodynamic activity towards human lung cancer cell-line A549 than their free-base precursors. Our results strongly suggest that incorporation of Zn(II) has improved the antiviral and anticancer properties of the nitroporphyrins. To the best of our knowledge, this is the first report demonstrating the dual activity of nitroporphyrin-zinc complexes as antiviral and anti-cancer, which will aid in their development as therapeutics in clinics.
Assuntos
Antineoplásicos/farmacologia , Inibidores da Fusão de HIV/farmacologia , Metaloporfirinas/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Zinco/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Antineoplásicos/toxicidade , Células CHO , Linhagem Celular Tumoral , Cricetulus , Fluorescência , Células HEK293 , Inibidores da Fusão de HIV/síntese química , Inibidores da Fusão de HIV/efeitos da radiação , Inibidores da Fusão de HIV/toxicidade , HIV-1/efeitos dos fármacos , Humanos , Luz , Metaloporfirinas/síntese química , Metaloporfirinas/efeitos da radiação , Metaloporfirinas/toxicidade , Estrutura Molecular , Nitrobenzenos/síntese química , Nitrobenzenos/farmacologia , Nitrobenzenos/efeitos da radiação , Nitrobenzenos/toxicidade , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidadeRESUMO
Non-symmetrically substituted four-ring achiral bent-core compounds with polar substituents, i.e.., chloro in the bent or transverse direction in the central core and cyano in the lateral direction at one terminal end of the molecule, are designed and synthesized. These molecules possess an alkoxy chain attached at only one end of the bent-core molecule. The molecular structure characterization is consistent with data from elemental and spectroscopic analysis. The materials thermal behaviour and phase characterization have been investigated by differential scanning calorimetry and polarizing microscopy. All the compounds exhibit a wide-ranging monotropic nematic phase.