Almeida Sinara Mônica Vitalino de, Lafayette Elizabeth Almeida, Silva Willams Leal, Lima Serafim Vanessa de, Menezes Thais Meira, Neves Jorge Luiz, Ruiz Ana Lucia Tasca Gois, Carvalho João Ernesto de, Moura Ricardo Olímpio de, Beltrão Eduardo Isidoro Carneiro, Carvalho Júnior Luiz Bezerra de, Lima Maria do Carmo Alves de
Laboratório de Imunopatologia Keizo Asami (LIKA) and Departamento de Bioquímica, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil; Faculdade de Ciências, Educação e Tecnologia de Garanhuns (FACETEG), Universidade de Pernambuco (UPE), Garanhuns 55290-000, PE, Brazil.
Laboratório de Química e Inovação Terapêutica (LQIT) - Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil.
Int J Biol Macromol. 2016 Nov;92:467-475. doi: 10.1016/j.ijbiomac.2016.07.057. Epub 2016 Jul 18.
Two new spiro-acridines were synthesized by introducing cyano-N-acylhydrazone between the acridine and phenyl rings followed by spontaneous cyclization. The final compounds (E)-1'-(benzylideneamino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-01) and (E)-1'-((4-methoxybenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-02) were evaluated for their interactions with calf thymus DNA, antiproliferative and human topoisomerase I and IIα inhibitory activities. Both compounds presented ability to bind DNA. The binding constant determined by UV-vis spectroscopy was found to be 10M. Antiproliferative assay demonstrated that AMTAC-01 and AMTAC-02 were most active against prostate and melanoma tumor cell lines, respectively. The compound did not present Topo I inhibitory activity. However, both derivatives displayed topoisomerase IIα inhibitory activity comparable to amsacrine, and AMTAC-02 was more potent than AMTAC-01 with methoxy substituent group on phenyl ring. This study demonstrates that the new derivatives are promising molecules with topoisomerase IIα inhibitory and antiproliferative activities.
通过在吖啶环和苯环之间引入氰基 -N- 酰腙，然后自发环化，合成了两种新的螺吖啶。对最终化合物（E）-1'-（亚苄基氨基）-5'-氧代-1'，5'-二氢-10H-螺[吖啶-9，2'-吡咯]-4'-腈（AMTAC-01）和（E）-1'-（（4-甲氧基亚苄基）氨基）-5'-氧代-1'，5'-二氢-10H-螺[吖啶-9，2'-吡咯]-4'-腈（AMTAC-02）与小牛胸腺DNA的相互作用、抗增殖活性以及对人拓扑异构酶I和IIα的抑制活性进行了评估。两种化合物均具有结合DNA的能力。通过紫外可见光谱法测定的结合常数为10M。抗增殖试验表明，AMTAC-01和AMTAC-02分别对前列腺癌和黑色素瘤肿瘤细胞系最具活性。该化合物没有表现出拓扑异构酶I抑制活性。然而，两种衍生物均表现出与安吖啶相当的拓扑异构酶IIα抑制活性，并且带有苯环甲氧基取代基的AMTAC-02比AMTAC-01更有效。这项研究表明，这些新衍生物是具有拓扑异构酶IIα抑制和抗增殖活性的有前景的分子。
