RESUMEN
A series of new oxoaporphine derivatives were synthesized and their inhibitory activity of topoisomerase I, cytotoxicity and DNA-binding properties were studied. Oxoaporphine can strongly inhibit topoisomerase I at concentrations of 5-50 µM and the cytotoxicity of the derivatives are more potent than their lead compound. Hypochromism, broadening and red shift in the absorption spectra were observed when these compounds bind to calf thymus DNA (CT DNA). These spectral characteristics were consistent with the intercalative binding of these compounds.
Asunto(s)
Alcaloides/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Aporfinas/farmacología , ADN-Topoisomerasas de Tipo I/metabolismo , ADN/efectos de los fármacos , Diseño de Fármacos , Inhibidores de Topoisomerasa I/farmacología , Alcaloides/síntesis química , Alcaloides/química , Animales , Antineoplásicos/química , Aporfinas/síntesis química , Aporfinas/química , Bovinos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Células MCF-7 , Estructura Molecular , Relación Estructura-Actividad , Inhibidores de Topoisomerasa I/síntesis química , Inhibidores de Topoisomerasa I/química , Células Tumorales CultivadasRESUMEN
The underlying hole-transfer mechanism in high-efficiency OSC bulk heterojunctions based on acceptor-donor-acceptor (A-D-A) nonfullerene acceptors (NFAs) remains unclear. Herein, we study the hole-transfer process between copolymer donor J91 and five A-D-A NFAs with different highest occupied molecular orbital energy offsets (ΔEH) (0.05-0.42 eV) via ultrafast optical spectroscopies. Transient absorption spectra reveal a rapid hole-transfer rate with small ΔEH, suggesting that a large energy offset is not required to overcome the exciton binding energy. Capacitance-frequency spectra and time-resolved photoluminescence spectra confirm the delocalization of an A-D-A-structured acceptor exciton with weak binding energy. Relative to the hole-transfer rate, hole-transfer efficiency is the key factor affecting device performance. We propose that holes primarily stem from weakly bound acceptor exciton dissociation, revealing a new insight into the hole-transfer process in A-D-A NFA-based OSCs.