RESUMO
A phytochemical investigation of the methanolic extract of the bark of Endiandra kingiana led to the isolation of seven new tetracyclic endiandric acid analogues, kingianic acids A-G (1-7), together with endiandric acid M (8), tsangibeilin B (9) and endiandric acid (10). Their structures were determined by 1D- and 2D-NMR analysis in combination with HRMS experiments. The structure of compounds 9 and 10 were confirmed by single-crystal X-ray diffraction analysis. These compounds were screened for Bcl-xL and Mcl-1 binding affinities and cytotoxic activity on various cancer cell lines. Compound 5 showed moderate cytotoxic activity against human colorectal adeno-carcinoma (HT-29) and lung adenocarcinoma epithelial (A549) cell lines, with IC50 values in the range 15-17 µM, and compounds 3, 6 and 9 exhibited weak binding affinity for the anti-apoptotic protein Mcl-1.
Assuntos
Ácidos Carboxílicos/química , Lauraceae/química , Estrutura Molecular , Extratos Vegetais/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Humanos , Extratos Vegetais/farmacologia , Difração de Raios XRESUMO
In the title compound, C(13)H(13)N(5)OS·H(2)O, the thio-urea mol-ecules closely resemble each other and are approximately planar; the dihedral angles formed between the terminal benzene rings are 7.88â (8) and 7.20â (8)°, respectively. The observed planarity correlates with the presence of bifurcated N-Hâ¯(O,N) hydrogen bonds. In the crystal, the mol-ecules are connected into supra-molecular double chains via a combination of N-Hâ¯S (linking the two independent mol-ecules), O-Hâ¯O and O-Hâ¯N (linking dimeric aggregates into a supra-molecular chain via hy-droxy-water, water-water and water-pyrazine inter-actions) and O-Hâ¯S hydrogen bonds (connecting two chains). The chains are further connected by C-Hâ¯N and C-Hâ¯S inter-actions.