Characterization and Antiproliferative Activity of a Novel 2-Aminothiophene Derivative-β-Cyclodextrin Binary System
Elayne Barros Ferreira,
Walter Ferreira da Silva Júnior,
Jonas Gabriel de Oliveira Pinheiro,
Aldilane Gonçalves da Fonseca,
Telma Maria Araújo Moura Lemos,
Hugo Alexandre de Oliveira Rocha,
Eduardo Pereira de Azevedo,
Francisco Jaime Bezerra Mendonça Junior,
Ádley Antonini Neves de Lima
Affiliations
Elayne Barros Ferreira
Department of Pharmacy, Federal University of Rio Grande do Norte, Av. General Cordeiro de Farias, s/n, Petrópolis, Natal, Rio Grande do Norte 59012-570, Brazil
Walter Ferreira da Silva Júnior
Department of Pharmacy, Federal University of Rio Grande do Norte, Av. General Cordeiro de Farias, s/n, Petrópolis, Natal, Rio Grande do Norte 59012-570, Brazil
Jonas Gabriel de Oliveira Pinheiro
Department of Pharmacy, Federal University of Rio Grande do Norte, Av. General Cordeiro de Farias, s/n, Petrópolis, Natal, Rio Grande do Norte 59012-570, Brazil
Aldilane Gonçalves da Fonseca
Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Av. General Cordeiro de Faria, s/n, Petrópolis, Natal, Rio Grande do Norte 59012-570, Brazil
Telma Maria Araújo Moura Lemos
Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Av. General Cordeiro de Faria, s/n, Petrópolis, Natal, Rio Grande do Norte 59012-570, Brazil
Hugo Alexandre de Oliveira Rocha
Department of Biochemistry, Federal University of Rio Grande do Norte, Av. Senador Salgado Filho, 3000, Lagoa Nova, Natal, Rio Grande do Norte 59078-970, Brazil
Eduardo Pereira de Azevedo
Graduate Program of Biotechnology, Laureate International Universities—Universidade Potiguar (UnP), Av. Sen. Salgado Filho, 1610, Lagoa Nova, Natal, Rio Grande do Norte 59056-000, Brazil
Francisco Jaime Bezerra Mendonça Junior
Department of Biological Sciences, State University of Paraíba, Rua Horácio Trajano de Oliveira, s/n, Cristo Redentor, João Pessoa 58071-160, Brazil
Ádley Antonini Neves de Lima
Department of Pharmacy, Federal University of Rio Grande do Norte, Av. General Cordeiro de Farias, s/n, Petrópolis, Natal, Rio Grande do Norte 59012-570, Brazil
The novel 2-aminothiophene derivative 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN) has shown potential anti-proliferative activity in human cancer cell lines. However, the poor aqueous solubility of 6CN impairs its clinical use. This work aimed to develop binary 6CN-β-cyclodextrin (βCD) systems with the purpose of increasing 6CN solubility in water and therefore, to improve its pharmacological activity. The 6CN-βCD binary systems were prepared by physical mixing, kneading and rotary evaporation methods and further characterized by FTIR, XRD, DSC, TG and SEM. In addition, molecular modeling and phase solubility studies were performed. Finally, MTT assays were performed to investigate the cytostatic and anti-proliferative effects of 6CN-βCD binary systems. The characterization results show evident changes in the physicochemical properties of 6CN after the formation of the binary systems with βCD. In addition, 6CN was associated with βCD in aqueous solution and the solid state, which was confirmed by molecular modeling and the aforementioned characterization techniques. Phase solubility studies indicated that βCD forms stable 1:1 complexes with 6CN. The MTT assay demonstrated the cytostatic and anti-proliferative activities of 6CN-βCD binary systems and therefore, these might be considered as promising candidates for new anticancer drugs.
