The Crystal and Molecular Structure of Staurosporine, a New Alkaloid from a Streptomyces Strain

Abstract

The molecular sturcture of staurosporine, an alkaloid from a Streptomyces strain, has been determined by means of an X-ray crystallographic analysis of its methanol solvate (C28H26N4O3·CH3OH). The crystals are monoclinic, with four formula units in a unit cell with dimensions of a=23.487(6), b=7.636(3), c=15.638(4) Å, and β=116.71(5)°; the space group is C2. 2532 unique intensity data were collected on a four-circle diffractometer with LiF-monochromated Cu Kα radiation. The structure was solved by the Monte Carlo direct method, using the 20 strongest reflections as the starting set; the 72nd random phase set led to the correct solution. The R value reached 0.047 by block-diagonal least-squares refinements. Staurosporine has been found to contain a unique dimeric indole structure. Because of the steric hindrance, the indolo[2,3-a]carbazole aromatic system in the molecule is slightly bent; the two terminal benzene rings make an angle of 7.5° with each other.

4,5-Dianilinophthalimide: a protein-tyrosine kinase inhibitor with selectivity for the epidermal growth factor receptor signal transduction pathway and potent in vivo antitumor activity.

“…1) revealed an asymmetric propeller-shaped conformation, which is probably due to a subtle balance of steric and electronic factors. The conformation of DAPH 1 in the crystal structure differs from that of the staurosporine aglycone, which is a planar molecule (29). We believe that this conformation is responsible for the different selectivity profile of DAPHs for inhibition of protein kinases.…”

Structure of the protein tyrosine kinase domain of C-terminal Src kinase (CSK) in complex with staurosporine 1 1Edited by I. A. Wilson

“…The structure has been further re®ned to the crystallographic R-factor of 19.9 % (R free 28.7 %) at 2.4 A Ê resolution. Geometric restraints for staurosporine, which were used throughout the re®nement, were generated using the staurosporine coordinates (Furusaki et al, 1982) in the Cambridge structural database (Allen & Kennard, 1993).…”

A Novel Small Molecular Weight Compound with a Carbazole Structure That Demonstrates Potent Human Immunodeficiency Virus Type-1 Integrase Inhibitory Activity

“…Other carbazole derivatives have demonstrated various other activities, such as topoisomerase inhibition (Marotto et al, 2002;Facompre et al, 2002;Carrasco et al, 2001), hypotensive activity (Furusaki et al, 1982), platelet aggregation inhibition (Oka et al, 1986), and anti-fungal activity (Sunthitikawinsakul et al, 2003). In this report we present another possible activity of carbazole derivatives, that of HIV-1 integrase inhibitor.…”

“…Staurosporine, discovered among microbial alkaloids, was the first carbazole derivative reported to demonstrate biological activity (Omura et al, 1977;Furusaki et al, 1978;Furusaki et al, 1982), which was protein kinase C inhibition (Tamaoki et al, 1986).…”