Muthusamy Jayaraman - Academia.edu (original) (raw)
Papers by Muthusamy Jayaraman
ACS Chemical Biology, 2013
We evaluated the abilities of an antisense oligonucleotide (ASO), a small interfering RNA (siRNA)... more We evaluated the abilities of an antisense oligonucleotide (ASO), a small interfering RNA (siRNA), and a single-stranded siRNA (ss-siRNA) to inhibit expression from the PTEN gene in mice when formulated identically with lipid nanoparticles (LNPs). Significantly greater reductions in levels of PTEN mRNA were observed for LNP-formulated agents compared to unformulated drugs when gene silencing was evaluated after a single dose in the livers of mice. An unformulated ss-siRNA modified with a metabolically stable phosphate mimic 5'-(E)-vinylphosphonate showed dose-dependent reduction of PTEN mRNA in mice, albeit at doses significantly higher than those observed for formulated ss-siRNA. These results demonstrate that LNPs can be used to deliver functional antisense and ss-siRNA therapeutics to the liver, indicating that progress in the field of siRNA delivery is transferable to other classes of nucleic acid-based drugs.
Tetrahedron Letters
A convenient approach to densely functionalized α-allyl-β-lactams has been developed using organo... more A convenient approach to densely functionalized α-allyl-β-lactams has been developed using organometallic reagents and α-keto-β-lactams. Indium mediated Barbier reaction in aqueous media proceeded with a higher level of diastereoselectivity and chemical yield than zinc mediated Barbier reaction in anhydrous organic solvents.
Tetrahedron Letters
A convenient approach to densely functionalized α-allyl-β-lactams has been developed using organo... more A convenient approach to densely functionalized α-allyl-β-lactams has been developed using organometallic reagents and α-keto-β-lactams. Indium mediated Barbier reaction in aqueous media proceeded with a higher level of diastereoselectivity and chemical yield than zinc mediated Barbier reaction in anhydrous organic solvents.
Tetrahedron, 1996
ABSTRACT
ChemInform, 1996
heterocyclic 4-membered rings heterocyclic 4-membered rings R 0055
ChemInform
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.
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.
Tetrahedron Letters, 1996
Antibiotics belonging to the families of penicillins, cephalosporins, eephamycins, nocardicins an... more Antibiotics belonging to the families of penicillins, cephalosporins, eephamycins, nocardicins and monobactams have in common an c~-amino-13-1actam moiety) Diversely substituted 3-amino-2-azetidinones can serve as synthons for such antibiotics as well as, amino sugars, alkaloids, and other natural products)
![Research paper thumbnail of ChemInform Abstract: Synthesis of New Indeno[1,2-c]isoquinolines: Cytotoxic Non-Camptothecin Topoisomerase I Inhibitors](https://attachments.academia-assets.com/44507100/thumbnails/1.jpg)
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ChemInform, 1999
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.
Tetrahedron Letters, 1997
A convenient approach to densely functionalized α-allyl-β-lactams has been developed using organo... more A convenient approach to densely functionalized α-allyl-β-lactams has been developed using organometallic reagents and α-keto-β-lactams. Indium mediated Barbier reaction in aqueous media proceeded with a higher level of diastereoselectivity and chemical yield than zinc mediated Barbier reaction in anhydrous organic solvents.
Tetrahedron, 1996
The homochiral β-lactams described in the preceding paper undergone an acid catalyzed rearrangeme... more The homochiral β-lactams described in the preceding paper undergone an acid catalyzed rearrangement to 4-aminopyrrolidinones 2a-e in excellent yields. A diastereoselective synthesis of cis,cis-bis-β-lactams 13 & 14 has been achieved by using imines bearing a β-lactam back bone in good yields and good to excellent selectivities.
Tetrahedron, 1996
... G.; Ohno. M., Eds.; SpringerVedag: Berlin, 1990, p 565. (d) Van der Steen, FH; Van Koten, G. ... more ... G.; Ohno. M., Eds.; SpringerVedag: Berlin, 1990, p 565. (d) Van der Steen, FH; Van Koten, G. Tetrahedron 1991, 47, 7503. (e) Durckheimer, W.; Blumbach, J.; Latrell, R.; Sheunemann, KH Angew. Chem., Int. Ed. ... Rev. 1989, 89, 1447. (e) Brown, MJ Heterocycles 1989, 29, 2225. ...
The Journal of Organic Chemistry, 1994
The Journal of Organic Chemistry, 1998
![Research paper thumbnail of Synthesis of New Dihydroindeno[1,2- c ]isoquinoline and Indenoisoquinolinium Chloride Topoisomerase I Inhibitors Having High in Vivo Anticancer Activity in the Hollow Fiber Animal Model](https://attachments.academia-assets.com/44507096/thumbnails/1.jpg)
](Journal of Medicinal Chemistry, 2002
Journal of Medicinal Chemistry, 1999
A number of indenoisoquinolines were prepared and evaluated for cytotoxicity in human cancer cell... more A number of indenoisoquinolines were prepared and evaluated for cytotoxicity in human cancer cell cultures and for activity vs topoisomerase 1 (top1). The two most cytotoxic indenoisoquinolines proved to be cis-6-ethyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8, 9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (21) and cis-6-allyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8, 9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (22), both of which displayed submicromolar mean graph midpoints when tested in 55 human cancer cell cultures. Two of the most potent top1 inhibitors were 6-(3-carboxy-1-propyl)-5,6-dihydro-5, 11-dioxo-11H-indeno[1,2-c]isoquinoline (26) and 6-ethyl-2, 3-dimethoxy-8,9-(methylenedioxy)-11H-indeno[1,2-c]isoquinolinium chloride (27), both of which also inhibited top2, unwound DNA, and are assumed to be DNA intercalators. However, two additional potent top1 inhibitors, 6-allyl-5,6-dihydro-2,3-dimethoxy-8, 9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (13c) and 5,6-dihydro-6-(4-hydroxybut-1-yl)-2,3-dimethoxy-8, 9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (19a), did not unwind DNA and did not affect top2. Some of the DNA cleavage sites detected in the presence of the indenoisoquinolines were different from those seen with the camptothecins. The cleavage sites induced by the indenoisoquinolines were reversed by salt treatment, which is consistent with the reversible trapping of top1 cleavable complexes by the indenoisoquinolines. In general, the potencies of the indenoisoquinolines as top1 inhibitors did not correlate with their potencies as cytotoxic agents, as some of the most cytotoxic agents had little if any effect on top1. On the other hand, the most potent of the indenoisoquinolines vs top1 were not the most cytotoxic. In several cases, moderate activity was observed for both cytotoxicity and activity vs top1.
ACS Chemical Biology, 2013
We evaluated the abilities of an antisense oligonucleotide (ASO), a small interfering RNA (siRNA)... more We evaluated the abilities of an antisense oligonucleotide (ASO), a small interfering RNA (siRNA), and a single-stranded siRNA (ss-siRNA) to inhibit expression from the PTEN gene in mice when formulated identically with lipid nanoparticles (LNPs). Significantly greater reductions in levels of PTEN mRNA were observed for LNP-formulated agents compared to unformulated drugs when gene silencing was evaluated after a single dose in the livers of mice. An unformulated ss-siRNA modified with a metabolically stable phosphate mimic 5'-(E)-vinylphosphonate showed dose-dependent reduction of PTEN mRNA in mice, albeit at doses significantly higher than those observed for formulated ss-siRNA. These results demonstrate that LNPs can be used to deliver functional antisense and ss-siRNA therapeutics to the liver, indicating that progress in the field of siRNA delivery is transferable to other classes of nucleic acid-based drugs.
Tetrahedron Letters
A convenient approach to densely functionalized α-allyl-β-lactams has been developed using organo... more A convenient approach to densely functionalized α-allyl-β-lactams has been developed using organometallic reagents and α-keto-β-lactams. Indium mediated Barbier reaction in aqueous media proceeded with a higher level of diastereoselectivity and chemical yield than zinc mediated Barbier reaction in anhydrous organic solvents.
Tetrahedron Letters
A convenient approach to densely functionalized α-allyl-β-lactams has been developed using organo... more A convenient approach to densely functionalized α-allyl-β-lactams has been developed using organometallic reagents and α-keto-β-lactams. Indium mediated Barbier reaction in aqueous media proceeded with a higher level of diastereoselectivity and chemical yield than zinc mediated Barbier reaction in anhydrous organic solvents.
Tetrahedron, 1996
ABSTRACT
ChemInform, 1996
heterocyclic 4-membered rings heterocyclic 4-membered rings R 0055
ChemInform
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.
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.
Tetrahedron Letters, 1996
Antibiotics belonging to the families of penicillins, cephalosporins, eephamycins, nocardicins an... more Antibiotics belonging to the families of penicillins, cephalosporins, eephamycins, nocardicins and monobactams have in common an c~-amino-13-1actam moiety) Diversely substituted 3-amino-2-azetidinones can serve as synthons for such antibiotics as well as, amino sugars, alkaloids, and other natural products)
ChemInform, 1999
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.
Tetrahedron Letters, 1997
A convenient approach to densely functionalized α-allyl-β-lactams has been developed using organo... more A convenient approach to densely functionalized α-allyl-β-lactams has been developed using organometallic reagents and α-keto-β-lactams. Indium mediated Barbier reaction in aqueous media proceeded with a higher level of diastereoselectivity and chemical yield than zinc mediated Barbier reaction in anhydrous organic solvents.
Tetrahedron, 1996
The homochiral β-lactams described in the preceding paper undergone an acid catalyzed rearrangeme... more The homochiral β-lactams described in the preceding paper undergone an acid catalyzed rearrangement to 4-aminopyrrolidinones 2a-e in excellent yields. A diastereoselective synthesis of cis,cis-bis-β-lactams 13 & 14 has been achieved by using imines bearing a β-lactam back bone in good yields and good to excellent selectivities.
Tetrahedron, 1996
... G.; Ohno. M., Eds.; SpringerVedag: Berlin, 1990, p 565. (d) Van der Steen, FH; Van Koten, G. ... more ... G.; Ohno. M., Eds.; SpringerVedag: Berlin, 1990, p 565. (d) Van der Steen, FH; Van Koten, G. Tetrahedron 1991, 47, 7503. (e) Durckheimer, W.; Blumbach, J.; Latrell, R.; Sheunemann, KH Angew. Chem., Int. Ed. ... Rev. 1989, 89, 1447. (e) Brown, MJ Heterocycles 1989, 29, 2225. ...
The Journal of Organic Chemistry, 1994
The Journal of Organic Chemistry, 1998
Journal of Medicinal Chemistry, 2002
Journal of Medicinal Chemistry, 1999
A number of indenoisoquinolines were prepared and evaluated for cytotoxicity in human cancer cell... more A number of indenoisoquinolines were prepared and evaluated for cytotoxicity in human cancer cell cultures and for activity vs topoisomerase 1 (top1). The two most cytotoxic indenoisoquinolines proved to be cis-6-ethyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8, 9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (21) and cis-6-allyl-5,6,12,13-tetrahydro-2,3-dimethoxy-8, 9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (22), both of which displayed submicromolar mean graph midpoints when tested in 55 human cancer cell cultures. Two of the most potent top1 inhibitors were 6-(3-carboxy-1-propyl)-5,6-dihydro-5, 11-dioxo-11H-indeno[1,2-c]isoquinoline (26) and 6-ethyl-2, 3-dimethoxy-8,9-(methylenedioxy)-11H-indeno[1,2-c]isoquinolinium chloride (27), both of which also inhibited top2, unwound DNA, and are assumed to be DNA intercalators. However, two additional potent top1 inhibitors, 6-allyl-5,6-dihydro-2,3-dimethoxy-8, 9-(methylenedioxy)-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (13c) and 5,6-dihydro-6-(4-hydroxybut-1-yl)-2,3-dimethoxy-8, 9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (19a), did not unwind DNA and did not affect top2. Some of the DNA cleavage sites detected in the presence of the indenoisoquinolines were different from those seen with the camptothecins. The cleavage sites induced by the indenoisoquinolines were reversed by salt treatment, which is consistent with the reversible trapping of top1 cleavable complexes by the indenoisoquinolines. In general, the potencies of the indenoisoquinolines as top1 inhibitors did not correlate with their potencies as cytotoxic agents, as some of the most cytotoxic agents had little if any effect on top1. On the other hand, the most potent of the indenoisoquinolines vs top1 were not the most cytotoxic. In several cases, moderate activity was observed for both cytotoxicity and activity vs top1.