Papers by ramesh samineni
iScience, 2022
To tackle the Covid-19 pandemic, governments need citizens to trust messages on behaviour change,... more To tackle the Covid-19 pandemic, governments need citizens to trust messages on behaviour change, and to support more draconian steps like lockdowns. Yet, lack of trust in public authority and a prevalence of rumours are shaping people's responses to the virus, especially in fragile, conflict-affected places. Action for Empowerment and Accountability (A4EA) research among poor and marginalised households in such areas shows how distrust causes serious problems -and how approaches tailored to local contexts can mitigate these. 1 Institute of Development Studies, Library Road, Brighton, BN1 9RE, United Kingdom +44 (0)1273 606261 ids.ac.uk IDS is a charitable company limited by guarantee and registered in England. Charity Registration Number 306371. Charitable Company Number 877338.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Scientific reports, Jan 21, 2015
In search for drugs to treat neuropsychiatric disorders wherein neurotrophic and neurogenic prope... more In search for drugs to treat neuropsychiatric disorders wherein neurotrophic and neurogenic properties are affected, two neurotrophically active small molecules specially crafted following natural product leads based on 2-oxa-spiro[5.5]-undecane scaffold, have been thoroughly evaluated for their neurotrophic, neurogenic and neuroprotective potential in ex vivo primary culture and in vivo zebrafish and mouse models. The outcome of in vivo investigations suggest that one of these molecules is more neurotrophic than neurogenic while the other one is more neurogenic than neurotrophic and the former exhibits remarkable neuroprotection in a mouse acute ischemic stroke model. The molecular mechanisms of action of these compounds appear to be through the TrkB-MEK-ERK-CREB-BDNF pathway as pre-treatment with neurotrophin receptor TrkB inhibitor ANA-12 and MEK inhibitor PD98059 attenuates the neurotrophic action of compounds.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
![Research paper thumbnail of A 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic](https://attachments.academia-assets.com/75224441/thumbnails/1.jpg)
Scientific Reports, May 4, 2017
Following our recent discovery of a new scaffold exhibiting significant neurotrophic and neurogen... more Following our recent discovery of a new scaffold exhibiting significant neurotrophic and neurogenic activities, a structurally tweaked analogue, embodying a 2-oxa-spiro [5.4]decane framework, has been conceptualised and found to be more potent and versatile. It exhibits enhanced neurotrophic and neurogenic action in in vitro, ex vivo and in vivo models and also shows robust neuroprotection in mouse acute cerebral stroke model. The observed attributes are traceable to the predominant activation of the TrkB-PI3K-AKT-CREB pathway. In addition, it also exhibits remarkable anti-neuroinflammatory activity by concurrently down-regulating pro-inflammatory cytokines IL-1α and IL-6, thereby providing a unique molecule with a trinity of neuroactivities, i.e. neurotrophic, neurogenic and anti-inflammatory. The new chemical entity disclosed here has the potential to be advanced as a versatile therapeutic molecule to treat stroke, depression, and possibly other neuropsychiatric disorders associated with attenuated neurotrophic/ neurogenic activity, together with heightened neuroinflammation. One of the major global health care challenges today is to tackle debilitating neurological and psychiatric disorders that affect mood or emotion, and cognitive functions 1, 2. The hallmarks of these diverse brain and behaviour disorders are neurodegeneration and/or altered neuroplasticity. Recent evidence highlight compromised neurotrophic and neurogenic characteristics on one hand and heightened neuroinflammation, on the other hand, associated with many central nervous system (CNS) disorders. The mood disorders that include depression, anxiety, post-traumatic stress disorder (PTSD), etc., are chronic debilitating CNS disorders, which in the long run also appear to cause cognitive decline 3, 4. The cognitive disorders, grouped together as 'dementia' , include diseases as diverse as Alzheimer's disease, frontotemporal dementia, vascular dementia (induced by acute and chronic vascular perturbations or ischemic stroke), etc., and are progressively neurodegenerative in nature 5-7. Another debilitating neurodegenerative condition is the cerebral ischemic stroke and the resultant vascular dementia cases are approaching an alarming level worldwide largely due to the lifestyle changes 8, 9. Acute ischemic stroke is one of the leading causes of death and long-term disability and the most unfortunate thing is the limited therapeutic
I-General Methods All reactions were carried out under argon or nitrogen atmosphere. TLC spots we... more I-General Methods All reactions were carried out under argon or nitrogen atmosphere. TLC spots were examined under UV light and revealed by sulfuric acid-anisaldehyde, KMnO 4 solution or phosphomolybdic acid. Dichloromethane was distilled from calcium hydride, tetrahydrofuran and diethylether were distilled from sodium/benzophenone, methanol was distilled over magnesium. CAUTION: all reactions involving Fe(CO) 5 have to be carried out under a well ventilated hood. These iron carbonyl-mediated reactions have been performed in usual pyrex glassware equipment. At the end of the reaction the residue of Fe(CO) 5 can be destroyed by addition of strong oxidizing agents such as Ce(NH 4) 2 (NO 3) 6 or FeCl 3. NMR spectra were obtained at 300 MHz or 500 MHz for 1 H and 75 MHz or 125MHz for 13 C with BRUCKER AVANCE 300 or 500 spectrometers. Chemical shifts are given in parts per million (δ) relative to chloroform (7.26 ppm) or benzene (7.16 ppm) residual peaks. Assignments of 1 H and 13 C resonances for complex structures were confirmed by extensive 2D experiments (COSY, HMQC, HMBC). Mass spectral analyses were performed at the Centre Régional de Mesures Physiques de l'Ouest (CRMPO) in Rennes (France). Rotation data were recorded on a Perkin-Elmer 241 Polarimeter. II Experimental procedures and characterizations II.1 Tetrahydro-6-vinylpyran-2-one (4a) O O To a solution 4-bromoorthobutyrate (764 µL, 4.40 mmol) in diethyl ether (12 mL) cooled at −78°C was added dropwise a solution of t-butylithium (5.24 mL, 7.86 mmol, 1.5 M in hexane). The cloudy mixture was stirred at −78°C for 1h and then at 0°C for 50 min. After recooling to −78°C, a solution of acrolein (120 µL, 1.57 mmol) in Et 2 O (3 mL) was added and
General methods: Unless otherwise noted, all reagents were used as received from commercial sourc... more General methods: Unless otherwise noted, all reagents were used as received from commercial sources. All air and moisture sensitive reactions were conducted under a nitrogen or argon atmosphere using flame-dried or oven-dried glassware with magnetic stirring. Anhydrous acetonitrile was prepared by stirring with P2O5, distilled and stored over 3Å molecular sieves prior to use. Tetrahydrofuran (THF) was dried over Na, benzophenone and distilled prior to use. Toluene was freshly distilled from CaH2 and used. Reactions were monitored by thin-layer chromatography carried out on silica plates (silica gel 60 F254, Merck) using UV-light, iodine and p-anisaldehyde for visualization. Column chromatography was carried out using silica gel (60-120 mesh or 100-200 mesh) packed in glass columns. Technical grade EtOAc and petroleum ether used for column chromatography were distilled prior to use. 1 H NMR and 13 C NMR spectra were recorded in CDCl3 as solvent on 300 MHz or 400 MHz or 500 MHz spectrometer at ambient temperature. The coupling constant J is given in Hz. The chemical shifts (δ) are reported in ppm on scale downfield from TMS and using the residual solvent peak in CDCl3 (H: δ = 7.26 and C: δ = 77.0 ppm) or TMS (δ = 0.0) as internal standard and signal patterns are indicated as follows: s = singlet, d = doublet, dd = doublet of doublet, dt = doublet of triplet, t = triplet, q = quartet, qd = quartet of doublet, m = multiplet, br = broad, tt = triplet of triplet. IR spectra were recorded on a Bruker Infrared spectrophotometer and are reported as cm-1. High-resolution mass spectra (HRMS) were recorded on a Waters-TOF spectrometer. 1. General procedure for the preparation of ynones (31a-f):
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Papers by ramesh samineni