Synthesis,DNA and protein interactions and human topoisomerase inhibition of novel Spiroacridine derivatives |
| |
Authors: | Rawny Galdino Gouveia Amélia Galdino Ribeiro Miguel Ângelo Santos Pinheiro Segundo Jamerson Ferreira de Oliveira Maria do Carmo Alves de Lima Túlio Ricardo Couto de Lima Souza Sinara Mônica Vitalino de Almeida Ricardo Olímpio de Moura |
| |
Institution: | 1. Laboratório de Síntese e Vetorização de Moléculas, Universidade Estadual da Paraíba, Departamento de Ciências Biológicas, João Pessoa, PB, Brazil;2. Laboratório de Química e Inovação Terapêutica (LQIT) – Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife, PE, Brazil;3. Unidade Acadêmica de Serra Talhada, Universidade Federal Rural de Pernambuco, Serra Talhada, PE, Brazil;4. Laboratório de Imunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco, Recife, PE, Brazil;5. Universidade de Pernambuco (UPE), Faculdade de Ciências, Educação e Tecnologia de Garanhuns (FACETEG), Garanhuns, PE, Brazil;6. Departamento de Ciências Farmacêuticas, Centro de Ciências Biológicas e da Saúde, Universidade Estadual da Paraíba – Bodocongó, Campina Grande, PB, Brazil |
| |
Abstract: | Nine new spiroacridine derivatives were synthetized by introducing cyano-N-acylhydrazone group between the acridine and phenyl-substituted rings followed by spontaneous cyclization. The new compounds were assayed for their DNA binding properties, human topoisomerase IIα inhibition and bovine serum albumin (BSA) interaction. Besides, docking analysis were performed in order to better understanding the biomolecule-compounds interactions. All compounds interacted with BSA which was demonstrated by the fluorescence suppression constant of 104?M?1. Compounds with chloro and NO2 substituents at that para-position on phenyl ring demonstrated the best results for BSA interaction. DNA binding constant determined by UV–vis data demonstrated high values for AMTAC-11 and AMTAC-14, 1.1?×?108?M?1 and 4.8?×?106?M?1, respectively, and all others presented constant values of 105?M?1. AMTAC-06 with chloro at para-position on phenyl ring presented a topoisomerase II inhibition of 84.34% in comparison to the positive controls used. Docking studies indicated that AMTAC-06 is able to intercalate the DNA base pairs at topoisomerase IIα active site, preventing DNA connection after break, in a process known as poisoning. Topoisomerase enzyme inhibition result was correlated to BSA interaction profile, since AMTAC-06 showed the best results in both analysis. The findings obtained here proved that methoxy or chloro substitution on phenyl ring at para-position is fundamental for in vitro activity of new spiroacridine derivatives, and indicates that AMTAC-06 is a promising entity and should serve as a lead compound in the development of new DNA and protein binders, as well as human topoisomerase II inhibitors. |
| |
Keywords: | Spiroacridine Protein interaction DNA-binding Topoisomerase IIα |
本文献已被 ScienceDirect 等数据库收录! |
|