Pedro-Hernández Luis D, Martínez-Klimova Elena, Martínez-Klimov Mark E, Cortez-Maya Sandra, Vargas-Medina Ana C, Ramírez-Ápan Teresa, Hernández-Ortega Simón, Martínez-García Marcos
Instituto de Quimica, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, Circuito Exterior, Coyoacan, C.P. 04510, Mexico D.F, Mexico.
Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, Circuito Exterior, Coyoacan, C.P. 04510, Mexico D.F, Mexico.
Anticancer Agents Med Chem. 2018;18(7):993-1000. doi: 10.2174/1871520618666171219114532.
The synthesis of conjugates of flutamide with resorcinarene-PAMAM-dendrimers as well as alkyl and ethyl phenyl chains in the lower part of the macrocycle as a nucleus and diethylenetriamines in the dendritic branches gives the opportunity to obtain conjugates in one step of synthesis with 16 and 64 flutamide moieties in the structure.
The in vitro anticancer studies showed that the conjugates of flutamide are more active than the free flutamide and the flutamide derivatives, thus diminishing the amount of flutamide used. The resorcinarenedendrimer- flutamide conjugates with a high drug payload improve the activity of the drug.
This is important in delivering a sufficient amount of flutamide and suggests that the dendrimer facilitates more of the drug being introduced into cells. It was also observed that the new conjugates are less toxic than the anti-androgens.
以间苯二酚芳烃 - PAMAM - 树枝状聚合物为基础，大环下部以烷基和乙基苯基链为核，树枝状分支以二亚乙基三胺为原料合成氟他胺共轭物，使得在一步合成中能够得到结构中含有16个和64个氟他胺部分的共轭物。
体外抗癌研究表明，氟他胺共轭物比游离氟他胺和氟他胺衍生物更具活性，从而减少了氟他胺的用量。具有高药物负载量的间苯二酚芳烃 - 树枝状聚合物 - 氟他胺共轭物提高了药物的活性。
这对于递送足够量的氟他胺很重要，表明树枝状聚合物有助于更多药物进入细胞。还观察到新的共轭物比抗雄激素毒性更小。
