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Biomedical subjects

P Prince

Publications and source records attributed to P Prince.

13 recordsLinked to original sources
PubMed2000

Novel hepatotrophic prodrugs of the antiviral nucleoside 9-(2-phosphonylmethoxyethyl)adenine with improved pharmacokinetics and antiviral activity.

The device of new hepatotrophic prodrugs of the antiviral nucleoside 9-(2-phosphonylmethoxyethyl)adenine (PMEA) with specificity for the asialoglycoprotein receptor on parenchymal liver cells is described. PMEA was conjugated to bi- and trivalent cluster glycosides (K(GN)(2) and K(2)(GN)(3), respectively) with nanomolar affinity for the asialoglycoprotein receptor. The liver uptake of the PMEA prodrugs was more than 10-fold higher than that of the parent drug (52+/-6% and 62+/-3% vs. 4.8+/-0.7% of the injected dose for PMEA) and could be attributed for 90% to parenchymal cells. Accumulation of the PMEA prodrugs in extrahepatic tissue (e.g., kidney, skin) was substantially reduced. The ratio of parenchymal liver cell-to-kidney uptake-a measure of the prodrugs therapeutic window-was increased from 0.058 +/- 0.01 for PMEA to 1.86 +/- 0.57 for K(GN)(2)-PMEA and even 2.69 +/- 0.24 for K(2)(GN)(3)-PMEA. Apparently both glycosides have a similar capacity to redirect (antiviral) drugs to the liver. After cellular uptake, both PMEA prodrugs were converted into the parent drug, PMEA, during acidification of the lysosomal milieu (t(1/2) approximately 100 min), and the released PMEA was rapidly translocated into the cytosol. The antiviral activity of the prodrugs in vitro was dramatically enhanced as compared to the parent drug (5- and 52-fold for K(GN)(2)-PMEA and K(2)(GN)(3)-PMEA, respectively). Given the 15-fold enhanced liver uptake of the prodrugs, we anticipate that the potency in vivo will be similarly increased. We conclude that PMEA prodrugs have been developed with greatly improved pharmacokinetics and therapeutic activity against viral infections that implicate the liver parenchyma (e.g., HBV). In addition, the significance of the above prodrug concept also extends to drugs that intervene in other liver disorders such as cholestasis and dyslipidemia.

Adenine↗
PubMed1990

1-Ethynyl-2,7-dimethoxynaphthalene: an example of hydrogen bonding between an ethynylic hydrogen and a methoxyl oxygen.

C14H12O2, Mr = 212.3, triclinic, P1, a = 6.6160 (12), b = 11.359 (2), c = 16.217 (2) A, alpha = 80.640 (11), beta = 86.305 (13), gamma = 78.858 (12) degrees, V = 1179.2 (4) A3, Z = 4, D chi = 1.196 g cm-3, lambda(Cu K alpha) = 1.54184 A, mu = 6.01 cm-1, F(000) = 448, T = 295 K, R = 0.039 for 3488 observations (of 4844 unique data). The crystal consists of two independent molecules related by a C--H...O contact. The donor is the ethynylic H on one molecule, and the acceptor is the methoxyl O ortho to the ethynylic group on the other molecule. The = C--H...O bond length (C to O distance) is 3.260 (2) A and the angle at H is 164 (1) degrees. The naphthalene ring system of the two independent molecules shows an average deviation from planarity of 0.007 (2) and 0.008 (2) A with respective maximum deviations of 0.015 (1) and 0.014 (2) A.

Hydrogen Bonding↗
PubMed1990

1-(1-chlorovinyl)-2,7-dimethoxynaphthalene.

C14H13ClO2, Mr = 248.71, monoclinic, P21/n, a = 11.291 (1), b = 7.343 (1), c = 15.223 (2) A, beta = 90.899 (8) degrees, V = 1262.0 (5) A3, Z = 4, Dx = 1.309 g cm-3, lambda(CU K alpha) = 1.54184 A, mu = 26.0 cm-1, F(000) = 520, T = 299 K, R = 0.041 for 2405 observations (of 2516 unique data). The average deviation from planarity is 0.019 (2) A with a maximum of 0.035 (1) A for the fused rings. The dihedral angle between the naphthalene system and the chlorovinyl group is 101.93 (4) degrees. The methoxy group ortho to the chlorovinyl adopts a conformation with the methyl group anti to the neighboring alpha carbon of the ring, with a C-C-O-C torsion angle of -175.6 (2) degrees. The other methoxy group has the methyl syn to the neighboring alpha carbon, with a C-C-O-C torsion angle of 1.9 (3) degrees.

Molecular Structure↗
PubMed1990

Diisopropylammonium chloride.

C6H16N+.Cl-,Mr = 137.65, orthorhombic, P2(1)2(1)2(1), a = 7.825 (4), b = 8.257 (1), c = 13.268 (2) A, V = 857.3 (5) A3, Z = 4, Dx = 1.066 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 3.6 cm-1, F(000) = 304, T = 295 K, R = 0.030 for 556 observations (of 901 unique data). Each H on the N atom is hydrogen bonded to a Cl atom. N--H...Cl bond lengths (N--Cl distance) are 3.180 (3) and 3.163 (3) A with N--H...Cl angles 176 (2) and 175 (2) degrees respectively. Each Cl atom is involved in two hydrogen bonds. The cation has an approximate twofold axis of symmetry.

Molecular Conformation↗
PubMed1989

2,7-Dimethoxynaphthalene.

C12H12O2, Mr = 188.2, orthorhombic, P2(1)2(1)2(1), a = 6.109 (3), b = 8.235 (2), c = 19.713 (3) A, V = 991.8 (9) A3, Z = 4, Dx = 1.260 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 0.79 cm-1, F(000) = 400, T = 293 K, R = 0.047 for 737 observations (of 1337 unique data). The average deviation from planarity is 0.013 (3) A with a maximum of 0.027 (3) A for the fused rings. Steric interaction between the methyl groups and the adjacent H atoms is responsible for opening the angles between the methoxyl groups and the rings. The CH3O-C-C angles are 125.5 (3) degrees [125.0 (3) degrees] where the methyl group is syn to the hydrogen, and 114.3 (3) degrees [114.2 (3) degrees] where it is anti.

Crystallization↗
PubMed1989

1-Acetyl-2,7-dimethoxynaphthalene.

C14H14O3, Mr = 230.3, monoclinic, P2(1)/c, a = 8.8107 (9), b = 18.372 (3), c = 7.7512 (11) A, beta = 98.49 (1) degrees, V = 1240.9 (5) A3, Z = 4, Dx = 1.232 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 0.80 cm-1, F(000) = 488, T = 293 K, R = 0.047 for 1909 observations (of 2848 unique data). The average deviation from planarity is 0.017 (2) A with a maximum of 0.0285 (15) A for the fused rings. The dihedral angle between the naphthalene system and the acetyl group is 117.91 (6) degrees. The methoxyl group ortho to the acetyl adopts a conformation with the methyl group anti to the neighboring alpha-carbon of the ring, with a C-C-O-C torsion angle of -178.7 (2) degrees. The other methoxyl group has the methyl syn to the neighboring alpha-carbon, with a C-C-O-C torsion angle of -1.3 (3) degrees.

Chemical Phenomena↗
PubMed1989

3-(2-Methoxyphenyl)-1H-2-benzopyran-1-one.

C16H12O3, Mr = 252.3, orthorhombic, Pna21, a = 6.633 (3), b = 13.367 (2), c = 14.056 (2) A, V = 1246.3 (9) A3, Z = 4, Dx = 1.344 g cm-3, lambda (Cu K alpha) = 1.54184 A, mu = 7.17 cm-1, F(000) = 528, T = 296 K, R = 0.027 for 2337 observations (of 2508 unique date). The average deviation from planarity is 0.013 (1) A with a maximum of 0.028 (1) A for the fused-rings system, and 0.003 (1) A with a maximum of 0.005 (1) A for the methoxyphenyl ring. The dihedral angle between the two systems is 4.7 (3) degrees. The methoxyphenyl ring is pushed away from the vinyl proton and towards the endocyclic O atom; the bond angles are 130.13 (9) and 110.13 (8) degrees, respectively.

Benzopyrans↗
PubMed1989

Methyl 3,4-dihydro-1-oxo-2(1H)-naphthylidenehydroxyacetate.

C13H12O4, Mr = 232.2, monoclinic, P2(1)/c, a = 8.499 (2), b = 13.798 (4), c = 9.652 (2) A, beta = 98.25 (2) degrees, V = 1120.1 (9) A3, Z = 4, Dx = 1.377 g cm-3, lambda(Cu K alpha) = 1.54184 A, mu = 8.12 cm-1, F(000) = 488, T = 295 K, R = 0.042 for 1916 observations (of 2296 unique data). The molecule contains an enol subunit, the hydroxy group of which forms an intramolecular hydrogen bond to the cyclic carbonyl group, with an O...O distance of 2.4782 (14) A and an O-H...O angle of 143 (3) degrees. The refined position of the hydrogen atom is 1.16 (4) A from the hydroxy oxygen and 1.44 (4) A from the carbonyl oxygen, and the isotropic thermal parameter is large; B = 13 (1) A2. The enol C = C bond distance is 1.371 (1) A and its C-OH distance is 1.312 (1) A.

Acetates↗
PubMed1988

Immunological evidence for differences in the exposed regions of OmpF porins from Escherichia coli B and K-12.

Nine monoclonal antibodies (MoF 0-8) directed against the native form (trimeric) of outer membrane protein OmpF of Escherichia coli B were obtained and characterized. All these antibodies bind to OmpF porin in intact E. coli B cells but not OmpF from E. coli K-12 cells which only differ at positions 66, 117 and 262 in the sequence. These antibodies exhibit a specificity to the native form, failing to recognize the denatured form in a liquid immunorecognition assay. Four tested antibodies are able to protect against colicin A, a bacteriotoxin using OmpF as receptor. One monoclonal antibody (MoF 0) is specific to the external topology of native porin in the outer membrane and three antibodies could recognize epitopes present in each conformation of subunits of trimer form. It is concluded that the region around the 66th and more probably around the 262nd amino acids are involved in cell-surface exposed epitopes. Moreover, these results support the assumption that the conformation of protruding regions of OmpF from E. coli B and K-12 are different.

Antibodies, Monoclonal↗
PubMed1988

[Technic of the peroperative use of Doppler in neurosurgery].

Intraoperative Doppler exploration during neurosurgery was used during treatment of intracranial aneurysms, arteriovenous malformations (AVM) and cerebral revascularization by extra-intra cranial anastomosis (EICA). It was also employed to study behavior of cortical arteries under different conditions. During treatment of aneurysms, Doppler can show, prior to clipping, whether blood flow through. The flow is regular--spasm of supply artery provokes acceleration of blood rate. After clipping it is possible to evaluate whether artery is still permeable without stenosis or torsion. In AVM, Doppler detects direction of blood. Flow and, in case of intraoperative embolization, confirms good exclusion of angiomatous nidus. Flow rate in cortical arteries was determined to verify reality of operative trauma under automatic retractors used in standard surgery. In EICA, Doppler provides precise data on exact localization of cutaneous incision centered on superficial temporal artery (STA) (longitudinal incision) and identifies its parietal branch. The artery in the cortical vessels with the lowest flow rate can be selected. After EICA it is possible to identify whether the donor artery is under spasm from the proximal clamp and whether or not the anastomosis is patent. When functioning is correct it can be defined whether there exists a preferential direction or a regular laminar distribution in T. In tumoral pathology, Doppler serves to identify arteries enclosed in lesion and therefore whether conservation is essential.

Cerebral Revascularization↗
PubMed1988

[Protection of the eyes in racket sports].

A survey was conducted on 1032 racket sport players from 10 randomly selected racket sport centers in Quebec during the month of October 1985. The use of protective eye glasses was found to be higher in racketball (70.2%) and squash (45.8%) than in badminton (8.8%) or tennis (3.5%). While a little less than 60% of protective eye glasses were equipped with unbreakable lenses, 40% of protective glasses were simple eye guards, containing no lens at all. Hence a large number of players assumed that they had adequate protection while wearing simple eye guards or their everyday normal glasses. Gender differences did not seem to affect the use of protective eye glasses. A general observation was that the older the player the better the eye protection, whereas novice players tended to be less prepared to use the protective glasses. The use of protective eye glasses was found to be compulsory in close to 46% of racketball centers and in 25% of squash clubs.

Adolescent↗