Crystal structure, Hirshfeld analysis and mol-ecular docking with the vascular endothelial growth factor receptor-2 of (3 Z)-5-fluoro-3-(hy-droxy-imino)-indolin-2-one

Bianca Barreto Martins; Leandro Bresolin; Renan Lira de Farias; Adriano Bof de Oliveira; Vanessa Carratu Gervini

doi:10.1107/S2056989017008301

Crystal structure, Hirshfeld analysis and mol-ecular docking with the vascular endothelial growth factor receptor-2 of (3 Z)-5-fluoro-3-(hy-droxy-imino)-indolin-2-one

Acta Crystallogr E Crystallogr Commun. 2017 Jun 7;73(Pt 7):987-992. doi: 10.1107/S2056989017008301. eCollection 2017 Jul 1.

Authors

Bianca Barreto Martins¹, Leandro Bresolin¹, Renan Lira de Farias², Adriano Bof de Oliveira³, Vanessa Carratu Gervini¹

Affiliations

¹ Universidade Federal do Rio Grande (FURG), Escola de Química e Alimentos, Rio Grande, Brazil.
² Universidade Estadual Paulista (UNESP), Instituto de Química, Araraquara, Brazil.
³ Universidade Federal de Sergipe (UFS), Departamento de Química, São Cristóvão, Brazil.

Abstract

The reaction between 5-fluoro-isatin and hydroxyl-amine hydro-chloride in acidic ethanol yields the title compound, C₈H₅FN₂O₂, whose mol-ecular structure matches the asymmetric unit and is nearly planar with an r.m.s. deviation for the mean plane through all non-H atoms of 0.0363 Å. In the crystal, the mol-ecules are linked by N-H⋯N, N-H⋯O and O-H⋯O hydrogen-bonding inter-actions into a two-dimensional network along the (100) plane, forming rings with R₂² (8) and R₁² (5) graph-set motifs. The crystal packing also features weak π-π inter-actions along the [100] direction [centroid-to-centroid distance 3.9860 (5) Å]. Additionally, the Hirshfeld surface analysis indicates that the major contributions for the crystal structure are the O⋯H (28.50%) and H⋯F (16.40%) inter-actions. An in silico evaluation of the title compound with the vascular endothelial growth factor receptor-2 (VEGFR-2) was carried out. The title compound and the selected biological target VEGFR-2 show the N-H⋯O(GLU94), (CYS96)N-H⋯O(isatine) and (PHE95)N-H⋯O(isatine) inter-molecular inter-actions, which suggests a solid theoretical structure-activity relationship.

Keywords: Hirshfeld surface analysis; crystal structure; isatin derivative–VEGFR-2 in silico evaluation.

Grants and funding

This work was funded by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior grant . Conselho Nacional de Desenvolvimento Científico e Tecnológico grant . Fundação de Amparo à Pesquisa do Estado de São Paulo grant . Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul grant .