RESUMO
An efficient pathway was disclosed for the synthesis of 3-chloro-6-nitro-1H-indazole derivatives by 1,3-dipolar cycloaddition on dipolarophile compounds 2 and 3. Faced the problem of separation of two regioisomers, a click chemistry method has allowed us to obtain regioisomers of triazole-1,4 with good yields from 82 to 90% were employed. Also, the antileishmanial biological potency of the compounds was achieved using an MTT assay that reported compound 13 as a promising growth inhibitor of Leishmania major. Molecular docking demonstrated highly stable binding with the Leishmania trypanothione reductase enzyme and produced a network of hydrophobic and hydrophilic interactions. Molecular dynamics simulations were performed for TryR-13 complex to understand its structural and intermolecular affinity stability in a biological environment. The studied complex remained in good equilibrium with a structure deviation of â¼1-3 Å. MM/GBSA binding free energies illustrated the high stability of TryR-13 complex. The studied compounds are promising leads for structural optimisation to enhance the antileishmanial activity.
Assuntos
Antiprotozoários/farmacologia , Inibidores Enzimáticos/farmacologia , Indazóis/farmacologia , Leishmania major/efeitos dos fármacos , Antiprotozoários/síntese química , Antiprotozoários/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Indazóis/síntese química , Indazóis/química , Leishmania major/enzimologia , Modelos Moleculares , Estrutura Molecular , NADH NADPH Oxirredutases/antagonistas & inibidores , NADH NADPH Oxirredutases/metabolismo , Testes de Sensibilidade Parasitária , Relação Estrutura-AtividadeRESUMO
In the title compound, C17H14N4O3, the indazole unit is planar to within 0.0171â (10)â Å and makes dihedral angles of 6.50â (6) and 6.79â (4)°, respectively, with the nitro and pendant phenyl groups. The conformation of the oxazole ring is best described as an envelope. In the crystal, oblique stacks along the a-axis direction are formed by π-π stacking inter-actions between the indazole unit and the pendant phenyl rings of adjacent mol-ecules. The stacks are linked into pairs through C-Hâ¯O hydrogen bonds. Hirshfeld surface analysis and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from Hâ¯H (36.3%), Oâ¯H/Hâ¯O (23.4%), Câ¯H/Hâ¯C (13.4%) and Nâ¯H/Hâ¯N (11.4%) inter-actions.
RESUMO
In the title compound, C19H23N3O8, the 5-nitro-2H-indazol-2-yl unit is almost planar, with the maximum deviation from the mean plane being 0.024â (2)â Å. The fused-ring system is nearly perpendicular to the three carboxyl-ate groups, with dihedral angles of 90.0â (3), 83.8â (1) and 80.4â (1)°. The ethyl groups attached to both ends of the propane chain are each disordered over two sets of sites, with site-occupancy ratios of 0.425â (17):0.575â (17) and 0.302â (15):0.698â (15). In the crystal, mol-ecules are linked by pairs of C-Hâ¯N hydrogen bonds, forming inversion dimers. The dimers are further linked by C-Hâ¯O hydrogen bonds, forming a three-dimensional network.
RESUMO
The fused five- and six-membered rings in the title mol-ecule, C10H9N3O2, are essentially coplanar, the largest deviation from the mean plane being 0.012â (1)â Å for the C atom linked to the nitro group. The fused-ring system makes a dihedral angle of 11.34â (6)° with the nitro group, leading to a syn-periplanar conformation. The plane through the atoms forming the allyl group is nearly perpendicular to the indazole fused-ring system, as indicated by the dihedral angle of 73.3â (5)°. In the crystal, each mol-ecule is linked to its symmetry equivalent about the center of inversion by pairs of non-classical C-Hâ¯O hydrogen bonds, forming an extended tape motif parallel to the (-12-1) plane.