Biomedical subjects
Publications and source records attributed to A Camerman.
Explore the source record for details and available documents.
The crystal structure of methionine-enkephalin has been determined by X-ray crystallography. There are two independent pentapeptides in the asymmetric unit and both display extended backbone conformations with their side chains arranged alternately below and above the backbone plane. The two molecules form a hydrogen-bonded head-to-tail dimer similar in conformation to one dimeric pair of leucine-enkephalin molecules in a previously reported crystal structure.
The molecular structure of quinespar, a quinazoline analogue of methotrexate and aminopterin, has been determined by X-ray crystallography. The molecule displays an extended conformation with the p-aminobenzoyl plane rotated 66 degrees from the plane of the quinazoline. The orientation of the quinazoline ring relative to the rest of the molecule is intermediate between the orientations of the comparable pteridine rings in folic acid and in DHFR-bound methotrexate. Evidence is presented to suggest that 2,4-diaminoquinazolines bind to DHFR in the same manner as do 2,4-diaminopteridines.
A series of 3-methyl-3-(m-hydroxyphenyl)piperidines with N-substituent variations have been synthesized and resolved, and an X-ray crystal structure of one analogue was determined. The compounds have been characterized, pharmacologically, by detailed opiate receptor binding studies and determination of in vivo analgesia and opiate antagonism. The results indicate that all compounds bind with high selectivity and moderate affinity to mu-receptors with no qualitative difference between enantiomeric pairs. By contrast a striking difference in activities is found, with the (-) enantiomers being pure agonists and the (+) enantiomers having both agonist and antagonist activity. The effect of N-substituents on relative agonist and antagonist potency does not mimic that of fused ring opiates with the N-phenethyl compound, the most potent antagonist. These results together with the X-ray structure obtained suggest that agonist and antagonist activity is initiated by a bimodel binding of the compounds in two different orientations at the mu-receptor site.
Explore the source record for details and available documents.
X-ray diffraction studies of crystals from samples of bimolane synthesized in China and in the United States showed that the crystals consist of the related compound ICRF-154. Analysis of the results of biological tests did not show any significant differences between the anticancer activity of bimolane and ICRF-154. It appears that the anticancer activity of bimolane is due to ICRF-154.
Explore the source record for details and available documents.
Molecular structures of two stereoisomers of 4-hydroperoxyisophosphamide (HPIPA) have been determined by single-crystal X-ray diffraction. These isomers are active cytostatic agents closely related to an active metabolite of the antitumor drug isophosphamide, an analogue of cyclophosphamide. Both isomers crystallize in monoclinic space group P21/c with cell dimensions for cis-HPIPA of a = 8.999 (2), b = 8.743 (2), c = 17.078 (4) A; beta = 107.91 (2) degrees, and Z = 4 molecules per unit cell, and cell dimensions for trans-HPIPA of a = 15.184 (3), b = 10.345 (3), c = 18.205 (3) A, beta = 114.15 (1) degrees, and Z = 8. The structures were solved by direct methods and refined by anisotropic least squares to a discrepancy index R = 0.048 for cis-HPIPA and R = 0.065 for trans-HPIPA. In both isomers the 4-hydroperoxy group is situated axial to the ring. The phosphoryl oxygen atom is situated axial to the ring and, thus, cis to the C(4) oxygen in the cis-HPIPA isomer. In the trans-HPIPA isomer, the phosphoryl oxygen is equatorial to the ring and trans to the C(4) oxygen.
Crystal structure determinations of C4-oxygen-substituted cytotoxic derivatives of the anticancer drug cyclophosphamide have all found the oxygen to be in the axial position, suggesting an inherent stability for this geometry. Recently, two isomeric bicyclic derivatives of 4-hydroperoxyisophosphamide (cyclized cis- and trans-HPIPA) have been obtained for which NMR coupling constants imply that the trans isomer has the C4-oxygen substituent in the equatorial position. Crystal structure determinations of both bicyclic compounds have now been performed. They show that the cis isomer has phosphoryl oxygen and C4-peroxy group both axial, similar to the conformation of the uncyclized HPIPA precursor and to the expectation based on NMR data; the trans isomer, however, has a phosphoryl oxygen equatorial, C4-peroxy group axial conformation, similar to its uncyclized HPIPA precursor but opposite in conformation at both positions to the NMR-based inferences. The oxazaphosphorinane ring in each isomer has a half-chair conformation, with the trans isomer probably flipping between two equally probable half-chairs; this disorder may account for the observed differences in the NMR C4-hydrogen coupling constants in the two isomers. The peroxy-containing ring adopts a chair conformation in both molecules.
A hydrogen-bonded complex of diphenylhydantoin (DPH) and 9-ethyladenine (EtAd) crystallizes from 2,4-pentanedione with the asymmetrical unit consisting of two DPH molecules, one EtAd molecule, and one solvent molecule. The crystal structure was solved by direct methods and refined to a residual of R = 0.054. Structure determination reveals that one DPH hydrogen-bonds to EtAd in a Watson-Crick scheme while the second DPH N(3)--H bonds to EtAd N(3) to form a 2:1 DPH-EtAd complex. Comparisons are made with barbiturate-adenine complexes and with an earlier postulation of a 1:1 DPH-EtAd complex derived from NMR and IR data. The 2,4-pentanedione molecule adopts the keto-enol configuration with an asymmetrical intramolecular hydrogen bond.
It is well-known that complex formation with copper ions increases the in vitro mycobactericidal action of the antituberculosis agent isoniazid. We report here the preparation and structure of a copper(II)-isoniazid complex. Unit cell parameters are a = 9.575, b = 14.855, and c = 7.056 A and space group P2(1)2(1)2(1). Copper bonding geometry is square planar with the isoniazid carbonyl oxygen and hydrazide amino nitrogen atoms and two chlorines occupying coordination positions. Complexing with copper(II) does not significantly alter the isoniazid molecular conformation.
Explore the source record for details and available documents.
The crystal and molecular structure of folic acid dihydrate has been determined by x-ray diffraction. Folic acid is in an extended conformation with the pteridine ring in the keto form. The C(4) oxygen and N(10) atoms are on the same side of the molecule, hydrogen-bonded to the same water. This conformation has the pteridine rotated approximately 180 degrees away from the orientation of the pteridine ring of methotrexate bound to dihydrofolate reductase. The folic acid pteridine and phenyl rings interact in a stacking manner which is suggestive of the type of associations these groups could form in a complex of folate, dihydrofolate reductase, and reduced nicotinamide adenine dinucleotide phosphate.
We have determined the molecular structure of the anticancer antiestrogen nafoxidine and compared its three-dimensional structure with two other clinically useful antiestrogens in order to delineate stereochemical parameters in these compounds. Crystals of nafoxidine hydrochloride-ethanol are monoclinic with cell dimensions a = 17.040, b = 7.967, c = 25.260 A, beta = 123.7 degrees, and space group P21/c with four formula units per cell. The structure was solved by direct phasing methods and refined to a discrepancy index of 0.068. The methoxyphenyl and phenyl rings are trans to each other relative to the ethylene bond, and the substituted amine-aryl ether chain has an extended conformation. Stereoscopic superposition drawings and tabular data are given to show structural similarities and difference in nafoxidine, clomiphene, and tamoxifen, the three antiestrogens with with demonstrated clinical efficacy in the management of metastatic mammary carcinoma.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.