Raymond Jones - Academia.edu (original) (raw)
Papers by Raymond Jones
Cheminform, Jul 31, 2001
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Cheminform, Jul 31, 2001
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Journal of the Chemical Society Perkin Transactions 1, 2000
Journal of the Chemical Society Perkin Transactions 1, 2000
ChemInform, 2010
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Journal of Medicinal Chemistry, Dec 1, 2001
Doxorubicin (Dox) can provide some stabilization in prostate cancer; however, its use is limited ... more Doxorubicin (Dox) can provide some stabilization in prostate cancer; however, its use is limited because of systemic toxicities, primarily cardiotoxicity and immunosuppression. The administration of a prodrug of doxorubicin, designed to permit selective activation by the tumor, would reduce general systemic exposure to the active drug and would thereby increase the therapeutic index. Prostate specific antigen (PSA) is a serine protease with chymotrypsin-like activity that is a member of the kallikrein gene family. PSA's putative physiological role is the liquefaction of semen by virtue of its ability to cleave the seminal fluid proteins semenogelins I and II. Serum PSA levels have been found to correlate well with the number of malignant prostate cells. The use of a prodrug which is cleaved by the enzyme PSA in the prostate should in principle produce high localized concentrations of the cytotoxic agent at the tumor site while limiting systemic exposure to the active drug. Cleavage maps following PSA treatment of human semenogelin were constructed. Systematic modification of the amino acid residues flanking the primary cleavage site led to the synthesis of a series of short peptides which were efficiently hydrolyzed by PSA. Subsequent coupling of selected peptides to doxorubicin provided a series of doxorubicin-peptide conjugates which were evaluated in vitro and in vivo as targeted prodrugs for PSA-secreting tumor cells. From these studies we selected Glutaryl-Hyp-Ala-Ser-Chg-Gln-Ser-Leu-Dox, 27, as the peptide-doxorubicin conjugate with the best profile of physical and biological properties. Compound 27 has a greater than 20-fold selectivity against human prostate PSA-secreting LNCaP cells relative to the non-PSA-secreting DuPRO cell line. In nude mouse xenograft studies, 27 reduced PSA levels by 95% and tumor weight by 87% at a dose below its MTD. Both doxorubicin and Leu-Dox (13) were ineffective in reducing circulating PSA and tumor burden at their maximum tolerated doses. On the basis of these results, we selected 27 for further study to assess its ability to inhibit human prostate cancer cell growth and tumorigenesis.
Synlett, 2011
ABSTRACT Orthogonally protected 3-(1-aminoalkyl)pyrazole- and 4,5-dihydropyrazole-5-carboxylic ac... more ABSTRACT Orthogonally protected 3-(1-aminoalkyl)pyrazole- and 4,5-dihydropyrazole-5-carboxylic acids are prepared by 1,3-dipolar cycloaddition of alpha-aminonitrile imines with electron-deficient alkenes; the pyrazole is incorporated into pseudotri- and tetrapeptides.
Cell Biology and Toxicology, Oct 1, 1990
were cultured for 7 days in a serum-free hormone supplemented medium. BE cells after 3 days in cu... more were cultured for 7 days in a serum-free hormone supplemented medium. BE cells after 3 days in culture were exposed to conditioned medium (CMt) from confluent BEAS-2B cells. By day 7, CMrtreated BE cells exhibited a lower colony forming efficiency (CFE), fewer cells per colony, and a reduced mitotic index (MI) and BrdU (bromodeoxyuridine) labeling index. CMt also enhanced the expression of a terminally differentiated squamous phenotype in BE cells. Cell free lysates from BEAS-2B eel& (CFLL) had effects similar to CMt on the MI and morphology of BE cells. In contrast, CMt and CFLt did not inhibit the growth, or alter the morphology of BEAS-2B cells. Conditioned medium from BE cells (CMQ did not reduce the growth of BEAS-2B eel&, and had little effect on the morphology of BE cells. In co-cultures, . 2. Key words: Bronchial epithelial cells, cell culture, communication, transforming growth factor-beta. 3. Abbreviations: BE = normal bronchial epithelial cells; BEAS-2B = adenovirus-12 SV40 hybrid virus transformed bronchial epithelial cells; CMn = conditioned medium from BE cells; CMt = conditioned medium from BEAS-2B cells; CFLn = cell free lysate from BE cells; CFLt = cell free lysate from BEAS-2B cells; BrdU = bromodeoxyuridine; KGM = keratinocyte growth medium; TGF-/~ = transforming growth factor type B; Albright, et al BE cells in direct contact with BEAS-2B cells had a lower MI (0.4-0.7 vs. 1.6%) compared with colonies of BE cells in these cocultures. The concentration of transforming growth factor beta (TGF-~) in conditioned media from BEAS-2B cells (CM O was increased lO-fold over that in CAIn. TGF-[3 is known to induce terminal differentiation in epithelial cells. These results suggest that the selective growth advantage of transformed cells over normal cells during human bronchial carcinogenesis may be related to the release of autocrine/paracrine factors (e.g., TGF-~) from transformed cells, which down-regulates and terminally differentiates the normal cells.
Cheminform, 2010
ABSTRACT 1,3-Dipolar cycloaddition of diazomethane to the α,β-unsaturated esters and lactones suc... more ABSTRACT 1,3-Dipolar cycloaddition of diazomethane to the α,β-unsaturated esters and lactones such as 2–4, 6–8, 10 and 13 occurs in a stereoselective manner affording conjugated . E and Z isomers of D-mannitol lead to identical product which was cyclised to investigate the absolute stereochemistry of the product. the regiospecificities of all the reactions are consistent with FMO coefficients obtained through AM1 calculations.
Tetrahedron, 2002
AbstractÐA new facile solid-phase synthesis of N,N 0 ,N 00 -substituted guanidines from an immobi... more AbstractÐA new facile solid-phase synthesis of N,N 0 ,N 00 -substituted guanidines from an immobilised amine component is described. The resin-bound amine was reacted with di-(2-pyridyl)thionocarbonate to generate the isothiocyanate which was treated with aryl/alkyl amines to yield the corresponding resin-bound thiourea. Desulfurisation of the thiourea was readily achieved by treatment with triphenylphosphine dichloride, and further reaction with aryl/alkyl amines followed by acidic cleavage with tri¯uoroacetic acid yielded N,N 0 ,N 00 -substituted guanidines of excellent purity and in good yield. q
Cheminform, Jul 31, 2001
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Cheminform, Jul 31, 2001
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Journal of the Chemical Society Perkin Transactions 1, 2000
Journal of the Chemical Society Perkin Transactions 1, 2000
ChemInform, 2010
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Journal of Medicinal Chemistry, Dec 1, 2001
Doxorubicin (Dox) can provide some stabilization in prostate cancer; however, its use is limited ... more Doxorubicin (Dox) can provide some stabilization in prostate cancer; however, its use is limited because of systemic toxicities, primarily cardiotoxicity and immunosuppression. The administration of a prodrug of doxorubicin, designed to permit selective activation by the tumor, would reduce general systemic exposure to the active drug and would thereby increase the therapeutic index. Prostate specific antigen (PSA) is a serine protease with chymotrypsin-like activity that is a member of the kallikrein gene family. PSA's putative physiological role is the liquefaction of semen by virtue of its ability to cleave the seminal fluid proteins semenogelins I and II. Serum PSA levels have been found to correlate well with the number of malignant prostate cells. The use of a prodrug which is cleaved by the enzyme PSA in the prostate should in principle produce high localized concentrations of the cytotoxic agent at the tumor site while limiting systemic exposure to the active drug. Cleavage maps following PSA treatment of human semenogelin were constructed. Systematic modification of the amino acid residues flanking the primary cleavage site led to the synthesis of a series of short peptides which were efficiently hydrolyzed by PSA. Subsequent coupling of selected peptides to doxorubicin provided a series of doxorubicin-peptide conjugates which were evaluated in vitro and in vivo as targeted prodrugs for PSA-secreting tumor cells. From these studies we selected Glutaryl-Hyp-Ala-Ser-Chg-Gln-Ser-Leu-Dox, 27, as the peptide-doxorubicin conjugate with the best profile of physical and biological properties. Compound 27 has a greater than 20-fold selectivity against human prostate PSA-secreting LNCaP cells relative to the non-PSA-secreting DuPRO cell line. In nude mouse xenograft studies, 27 reduced PSA levels by 95% and tumor weight by 87% at a dose below its MTD. Both doxorubicin and Leu-Dox (13) were ineffective in reducing circulating PSA and tumor burden at their maximum tolerated doses. On the basis of these results, we selected 27 for further study to assess its ability to inhibit human prostate cancer cell growth and tumorigenesis.
Synlett, 2011
ABSTRACT Orthogonally protected 3-(1-aminoalkyl)pyrazole- and 4,5-dihydropyrazole-5-carboxylic ac... more ABSTRACT Orthogonally protected 3-(1-aminoalkyl)pyrazole- and 4,5-dihydropyrazole-5-carboxylic acids are prepared by 1,3-dipolar cycloaddition of alpha-aminonitrile imines with electron-deficient alkenes; the pyrazole is incorporated into pseudotri- and tetrapeptides.
Cell Biology and Toxicology, Oct 1, 1990
were cultured for 7 days in a serum-free hormone supplemented medium. BE cells after 3 days in cu... more were cultured for 7 days in a serum-free hormone supplemented medium. BE cells after 3 days in culture were exposed to conditioned medium (CMt) from confluent BEAS-2B cells. By day 7, CMrtreated BE cells exhibited a lower colony forming efficiency (CFE), fewer cells per colony, and a reduced mitotic index (MI) and BrdU (bromodeoxyuridine) labeling index. CMt also enhanced the expression of a terminally differentiated squamous phenotype in BE cells. Cell free lysates from BEAS-2B eel& (CFLL) had effects similar to CMt on the MI and morphology of BE cells. In contrast, CMt and CFLt did not inhibit the growth, or alter the morphology of BEAS-2B cells. Conditioned medium from BE cells (CMQ did not reduce the growth of BEAS-2B eel&, and had little effect on the morphology of BE cells. In co-cultures, . 2. Key words: Bronchial epithelial cells, cell culture, communication, transforming growth factor-beta. 3. Abbreviations: BE = normal bronchial epithelial cells; BEAS-2B = adenovirus-12 SV40 hybrid virus transformed bronchial epithelial cells; CMn = conditioned medium from BE cells; CMt = conditioned medium from BEAS-2B cells; CFLn = cell free lysate from BE cells; CFLt = cell free lysate from BEAS-2B cells; BrdU = bromodeoxyuridine; KGM = keratinocyte growth medium; TGF-/~ = transforming growth factor type B; Albright, et al BE cells in direct contact with BEAS-2B cells had a lower MI (0.4-0.7 vs. 1.6%) compared with colonies of BE cells in these cocultures. The concentration of transforming growth factor beta (TGF-~) in conditioned media from BEAS-2B cells (CM O was increased lO-fold over that in CAIn. TGF-[3 is known to induce terminal differentiation in epithelial cells. These results suggest that the selective growth advantage of transformed cells over normal cells during human bronchial carcinogenesis may be related to the release of autocrine/paracrine factors (e.g., TGF-~) from transformed cells, which down-regulates and terminally differentiates the normal cells.
Cheminform, 2010
ABSTRACT 1,3-Dipolar cycloaddition of diazomethane to the α,β-unsaturated esters and lactones suc... more ABSTRACT 1,3-Dipolar cycloaddition of diazomethane to the α,β-unsaturated esters and lactones such as 2–4, 6–8, 10 and 13 occurs in a stereoselective manner affording conjugated . E and Z isomers of D-mannitol lead to identical product which was cyclised to investigate the absolute stereochemistry of the product. the regiospecificities of all the reactions are consistent with FMO coefficients obtained through AM1 calculations.
Tetrahedron, 2002
AbstractÐA new facile solid-phase synthesis of N,N 0 ,N 00 -substituted guanidines from an immobi... more AbstractÐA new facile solid-phase synthesis of N,N 0 ,N 00 -substituted guanidines from an immobilised amine component is described. The resin-bound amine was reacted with di-(2-pyridyl)thionocarbonate to generate the isothiocyanate which was treated with aryl/alkyl amines to yield the corresponding resin-bound thiourea. Desulfurisation of the thiourea was readily achieved by treatment with triphenylphosphine dichloride, and further reaction with aryl/alkyl amines followed by acidic cleavage with tri¯uoroacetic acid yielded N,N 0 ,N 00 -substituted guanidines of excellent purity and in good yield. q