E.s.r. studies on acylhydrazine and hydrazone copper(II) sulfate complexes

Summary Cu^II complexes of the [CuL₂(SO₄)]·nH₂O and [CuL(SO₄)(H₂O)₂]·nH₂O type, where L = benzoylhydrazine (PhCONHNH₂; BH) or iso-propanone benzoylhydrazone (PhCONHN:CMe₂; IBH), L= iso-nicotinoylhydrazine (NC₅H₄CONHNH₂; INH) or isopropanone iso-nicotinoylhydrazone (NC₅H₄CONHN: CMe₂; IINH); n = 0–2, were prepared and characterized by elemental analyses, molar conductances, and electronic, e.s.r. and i.r. spectral measurements. The electronic and e.s.r. spectra suggest a tetragonally distorted octahedral geometry in the solid state as well as in DMSO solution. The e.s.r. data also reveal an axial symmetry for most of the complexes in the solid state and in DMSO solution at 300 and 77 K, while the complex of IBH is isotropic at 300 K. The M_s = 2 transition observed for this complex suggests that it is a dimer. BH and INH bond to Cu^II through the C-O and NH₂ groups, whereas IBH and IINH bond through C-O and C-N groups.     

Chemistry and Biology of Cylindrols: Novel Inhibitors of Ras Farnesyl-Protein Transferase from Cylindrocarpon lucidum

Farnesyl-protein transferase (FPTase) is an enzyme responsible for the farnesylation of Ras protein. Farnesylation is required for cell-transforming activity in several tumor-types, and therefore, inhibition of FPTase activity may be a potential target for anticancer drugs. Our continued search for novel inhibitors led to the isolation of a number of bicyclic resorcinaldehyde cyclohexanone derivatives named here cylindrols A(1) to A(4), cylindrols B and B(1), and a number of known compounds, from Cylindrocarpon lucidum. The compounds were isolated by bioassay-guided separation using Sephadex LH-20, silica gel, and reverse phase HPLC. Structures were elucidated by extensive application of 2D NMR and X-ray crystallography. The determination of absolute stereochemistry was accomplished by CD measurements. Chemical transformations of the most abundant compound resulted in a number of key derivatives which were critical for the evaluation of structure activity relationship. These compounds are members of ascochlorin family and showed a wide range of inhibitory activity (0.7 &mgr;M to >140 &mgr;M) against FPTase. The FPTase activity was noncompetitive with respect to both substrates. Isolation, structures, chemical transformations, and FPTase activity are discussed in detail.     

A note on smoothed estimating functions

The kernel estimate of regression function in likelihood based models has been studied in Staniswalis (1989,J. Amer. Statist. Assoc.,84, 276–283). The notion of optimal estimation for the nonparametric kernel estimation of semimartingale intensity (t) is proposed. The goal is to arrive at a nonparametric estimate of ₀=(t ₀) for a fixed pointt ₀ [0, 1]. We consider the estimator that is a solution of the smoothed optimal estimating equation is the optimal estimating function as in Thavaneswaran and Thompson (1986,J. Appl. Probab.,23, 409–417).