Chiara Ghiron - Academia.edu (original) (raw)
Papers by Chiara Ghiron
Journal of acupuncture and meridian studies, Jan 22, 2018
This literature study paper will present the possibility of a correlation between the Energy Meri... more This literature study paper will present the possibility of a correlation between the Energy Meridians of Traditional Chinese Medicine (TCM), which can be traced back to the recently described Primo Vessels (formerly known as Bong-Han ducts), their composition and the ability of tumours to proliferate and metastasise. It is proposed that microvesicular bodies such as exosomes, known to be involved in cell-to-cell communication, immune response and tumour proliferation, could be moving across the body via the Primo Vascular System. The ubiquity of the Primo Vascular System and its penetration through the blood-brain barrier could also explain the ability of some peripheral tumours (e.g. breast tumour) to metastasise in the brain.
This literature study article will present the possibility of a correlation between the energy me... more This literature study article will present the possibility of a correlation between the energy meridians of Traditional Chinese Medicine, which can be traced back to the recently described primo vessels (formerly known as Bong-Han ducts), their composition, and the ability of tumors to proliferate and metastasize. It is proposed that microvesicular bodies such as exosomes, known to be involved in cell-to-cell communication, immune response, and tumor proliferation, could be moving across the body via the primo vascular system. The ubiquity of the primo vascular system and its penetration through the bloodebrain barrier could also explain the ability of some peripheral tumors (e.g., breast tumor) to metastasize in the brain.
Bioorganic & Medicinal Chemistry, 2009
Sodium (Na) channels continue to represent an important target for the development of novel antic... more Sodium (Na) channels continue to represent an important target for the development of novel anticonvulsants. We have synthesized and evaluated a series of 2,4(5)-diarylimidazoles for inhibition of the human neuronal Na V 1.2 Na channel isoform. Starting with the unsubstituted lead compound previously published 3, SAR studies were performed introducing substituents with different physico-chemical properties. Lipophilicity (log D 7.4 ) and basicity (pK a ) of the compounds were measured and submitted for QSPR investigations. Some of the active compounds described had IC 50 values that were considerably lower than our lead compound. In particular, the m-CF 3 disubstituted 22 was the most active compound, inhibiting hNa V 1.2 currents within the nanomolar concentration range (IC 50 = 200 nM). In comparison, lamotrigine and phenytoin, two clinically used anticonvulsant drugs known to inhibit Na channels, had IC 50 's values that were greater than 100 lM.
Bioorganic & Medicinal Chemistry Letters, 2008
A small family of novel 2,4(5)-diarylimidazoles were prepared through a simple and efficient synt... more A small family of novel 2,4(5)-diarylimidazoles were prepared through a simple and efficient synthesis and evaluated as potential inhibitors of hNa(v)1.2 sodium channel currents. One member of this series (4) exhibited profound inhibition of Na(v)1.2 currents, emerging as a promising lead compound for further structure-activity relationship studies for the development of novel sodium channel blockers.
Synlett, 2008
Abstract Using a commercially available device for controlled introduction of hydrogen in a vial ... more Abstract Using a commercially available device for controlled introduction of hydrogen in a vial for reactions under microwave dielectric heating, we developed a protocol for the transformation of substituted pyridines into the corresponding piperidines. Complete ...
Bioorganic & Medicinal Chemistry, 2008
A parallel synthesis of aryl azoles with neuroprotective activity is described. All compounds obt... more A parallel synthesis of aryl azoles with neuroprotective activity is described. All compounds obtained were evaluated in an in vitro assay using a NMDA toxicity paradigm showing a neuroprotective activity between 15% and 40%. The potential biological target of the active compounds was investigated by extensive literature searches based around similar scaffolds with reported neuroprotective activity. The most interesting molecules active in the NMDA toxicity assay (3a and 2g) showed moderate but significant activity in the inhibition of the Site 2 Sodium Channel binding assay at 10 lM. To confirm our hypothesis compounds 3a, c, f and 2g were tested in the Veratridine assay which is one of the excitotoxicity assays of revelance to NaV channels. The compounds tested showed an activity between 40% and 70%. The identification of neuroprotective small molecules and the identification of NaV channels as the potential site of action were the most important goals of this work.
European Journal of Organic Chemistry, 2008
An efficient synthesis of a pyrrolo-azepine scaffold for the parallel preparation of an array of ... more An efficient synthesis of a pyrrolo-azepine scaffold for the parallel preparation of an array of (oxo-pyrrolo-azepinyl)acetamides is described. The Stetter cyclisation of 1,3-cyclohexanedione with ethyl bromopyruvate was the key reaction in the assembly of a tetrahydrobenzofuran substrate which was submitted to a rapid transformation into a tetrahydroindole by microwave-assisted cyclocondensation in the presence of glycine. The carbonyl group was then stereoselectively transformed into the corresponding (Z)-oxime which
Sodium (Na) channels continue to represent an important target for the development of novel antic... more Sodium (Na) channels continue to represent an important target for the development of novel anticonvulsants. We have synthesized and evaluated a series of 2,4(5)-diarylimidazoles for inhibition of the human neuronal Na V 1.2 Na channel isoform. Starting with the unsubstituted lead compound previously published 3, SAR studies were performed introducing substituents with different physico-chemical properties. Lipophilicity (log D 7.4 ) and basicity (pK a ) of the compounds were measured and submitted for QSPR investigations. Some of the active compounds described had IC 50 values that were considerably lower than our lead compound. In particular, the m-CF 3 disubstituted 22 was the most active compound, inhibiting hNa V 1.2 currents within the nanomolar concentration range (IC 50 = 200 nM). In comparison, lamotrigine and phenytoin, two clinically used anticonvulsant drugs known to inhibit Na channels, had IC 50 's values that were greater than 100 lM.
![Research paper thumbnail of Novel Alpha-7 Nicotinic Acetylcholine Receptor Agonists Containing a Urea Moiety: Identification and Characterization of the Potent, Selective, and Orally Efficacious Agonist 1-[6-(4-Fluorophenyl)pyridin-3-yl]-3-(4-piperidin-1-ylbutyl) Urea (SEN34625/WYE-103914)](https://attachments.academia-assets.com/45497459/thumbnails/1.jpg)
](Journal of Medicinal Chemistry, 2010
Alpha-7 nicotinic acetylcholine receptor (R7 nAChR) agonists are promising therapeutic candidates... more Alpha-7 nicotinic acetylcholine receptor (R7 nAChR) agonists are promising therapeutic candidates for the treatment of cognitive impairment. We report a series of novel, potent small molecule agonists (4-18) of the R7 nAChR deriving from our continuing efforts in the areas of Alzheimer's disease and schizophrenia. One of the compounds of the series containing a urea moiety (16) was further shown to be a selective agonist of the R7 nAChR with excellent in vitro and in vivo profiles, brain penetration, and oral bioavailability and demonstrated in vivo efficacy in multiple behavioral cognition models. Structural modifications leading to the improved selectivity profile and the biological evaluation of this series of compounds are discussed.
Journal of acupuncture and meridian studies, Jan 22, 2018
This literature study paper will present the possibility of a correlation between the Energy Meri... more This literature study paper will present the possibility of a correlation between the Energy Meridians of Traditional Chinese Medicine (TCM), which can be traced back to the recently described Primo Vessels (formerly known as Bong-Han ducts), their composition and the ability of tumours to proliferate and metastasise. It is proposed that microvesicular bodies such as exosomes, known to be involved in cell-to-cell communication, immune response and tumour proliferation, could be moving across the body via the Primo Vascular System. The ubiquity of the Primo Vascular System and its penetration through the blood-brain barrier could also explain the ability of some peripheral tumours (e.g. breast tumour) to metastasise in the brain.
This literature study article will present the possibility of a correlation between the energy me... more This literature study article will present the possibility of a correlation between the energy meridians of Traditional Chinese Medicine, which can be traced back to the recently described primo vessels (formerly known as Bong-Han ducts), their composition, and the ability of tumors to proliferate and metastasize. It is proposed that microvesicular bodies such as exosomes, known to be involved in cell-to-cell communication, immune response, and tumor proliferation, could be moving across the body via the primo vascular system. The ubiquity of the primo vascular system and its penetration through the bloodebrain barrier could also explain the ability of some peripheral tumors (e.g., breast tumor) to metastasize in the brain.
Bioorganic & Medicinal Chemistry, 2009
Sodium (Na) channels continue to represent an important target for the development of novel antic... more Sodium (Na) channels continue to represent an important target for the development of novel anticonvulsants. We have synthesized and evaluated a series of 2,4(5)-diarylimidazoles for inhibition of the human neuronal Na V 1.2 Na channel isoform. Starting with the unsubstituted lead compound previously published 3, SAR studies were performed introducing substituents with different physico-chemical properties. Lipophilicity (log D 7.4 ) and basicity (pK a ) of the compounds were measured and submitted for QSPR investigations. Some of the active compounds described had IC 50 values that were considerably lower than our lead compound. In particular, the m-CF 3 disubstituted 22 was the most active compound, inhibiting hNa V 1.2 currents within the nanomolar concentration range (IC 50 = 200 nM). In comparison, lamotrigine and phenytoin, two clinically used anticonvulsant drugs known to inhibit Na channels, had IC 50 's values that were greater than 100 lM.
Bioorganic & Medicinal Chemistry Letters, 2008
A small family of novel 2,4(5)-diarylimidazoles were prepared through a simple and efficient synt... more A small family of novel 2,4(5)-diarylimidazoles were prepared through a simple and efficient synthesis and evaluated as potential inhibitors of hNa(v)1.2 sodium channel currents. One member of this series (4) exhibited profound inhibition of Na(v)1.2 currents, emerging as a promising lead compound for further structure-activity relationship studies for the development of novel sodium channel blockers.
Synlett, 2008
Abstract Using a commercially available device for controlled introduction of hydrogen in a vial ... more Abstract Using a commercially available device for controlled introduction of hydrogen in a vial for reactions under microwave dielectric heating, we developed a protocol for the transformation of substituted pyridines into the corresponding piperidines. Complete ...
Bioorganic & Medicinal Chemistry, 2008
A parallel synthesis of aryl azoles with neuroprotective activity is described. All compounds obt... more A parallel synthesis of aryl azoles with neuroprotective activity is described. All compounds obtained were evaluated in an in vitro assay using a NMDA toxicity paradigm showing a neuroprotective activity between 15% and 40%. The potential biological target of the active compounds was investigated by extensive literature searches based around similar scaffolds with reported neuroprotective activity. The most interesting molecules active in the NMDA toxicity assay (3a and 2g) showed moderate but significant activity in the inhibition of the Site 2 Sodium Channel binding assay at 10 lM. To confirm our hypothesis compounds 3a, c, f and 2g were tested in the Veratridine assay which is one of the excitotoxicity assays of revelance to NaV channels. The compounds tested showed an activity between 40% and 70%. The identification of neuroprotective small molecules and the identification of NaV channels as the potential site of action were the most important goals of this work.
European Journal of Organic Chemistry, 2008
An efficient synthesis of a pyrrolo-azepine scaffold for the parallel preparation of an array of ... more An efficient synthesis of a pyrrolo-azepine scaffold for the parallel preparation of an array of (oxo-pyrrolo-azepinyl)acetamides is described. The Stetter cyclisation of 1,3-cyclohexanedione with ethyl bromopyruvate was the key reaction in the assembly of a tetrahydrobenzofuran substrate which was submitted to a rapid transformation into a tetrahydroindole by microwave-assisted cyclocondensation in the presence of glycine. The carbonyl group was then stereoselectively transformed into the corresponding (Z)-oxime which
Sodium (Na) channels continue to represent an important target for the development of novel antic... more Sodium (Na) channels continue to represent an important target for the development of novel anticonvulsants. We have synthesized and evaluated a series of 2,4(5)-diarylimidazoles for inhibition of the human neuronal Na V 1.2 Na channel isoform. Starting with the unsubstituted lead compound previously published 3, SAR studies were performed introducing substituents with different physico-chemical properties. Lipophilicity (log D 7.4 ) and basicity (pK a ) of the compounds were measured and submitted for QSPR investigations. Some of the active compounds described had IC 50 values that were considerably lower than our lead compound. In particular, the m-CF 3 disubstituted 22 was the most active compound, inhibiting hNa V 1.2 currents within the nanomolar concentration range (IC 50 = 200 nM). In comparison, lamotrigine and phenytoin, two clinically used anticonvulsant drugs known to inhibit Na channels, had IC 50 's values that were greater than 100 lM.
Journal of Medicinal Chemistry, 2010
Alpha-7 nicotinic acetylcholine receptor (R7 nAChR) agonists are promising therapeutic candidates... more Alpha-7 nicotinic acetylcholine receptor (R7 nAChR) agonists are promising therapeutic candidates for the treatment of cognitive impairment. We report a series of novel, potent small molecule agonists (4-18) of the R7 nAChR deriving from our continuing efforts in the areas of Alzheimer's disease and schizophrenia. One of the compounds of the series containing a urea moiety (16) was further shown to be a selective agonist of the R7 nAChR with excellent in vitro and in vivo profiles, brain penetration, and oral bioavailability and demonstrated in vivo efficacy in multiple behavioral cognition models. Structural modifications leading to the improved selectivity profile and the biological evaluation of this series of compounds are discussed.
This is a conference presentation which I was invited to give in Chicago at the Natural Medicine ... more This is a conference presentation which I was invited to give in Chicago at the Natural Medicine Conference 2018 and is based on my recently published JAMS paper https://www.jams-kpi.com/article/S2005-2901(18)30075-X/fulltext.
Unfortunately the conference was cancelled due to dubious organisational practices, but I thought I'd share the presentation anyway.