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1.  Non-canonical regulation of phosphatidylinositol 3-kinase gamma isoform activity in retinal rod photoreceptor cells 
Phosphatidylinositol 3-Kinases (PI3Ks) are a family of lipid kinases that phosphorylate the D3-hydroxyls of the inositol ring of phosphoinositides, and are responsible for coordinating a diverse range of cellular functions. A canonical pathway of activation of PI3Ks through the interaction of RA-domain with Ras proteins has been well established. In retinal photoreceptors, we have identified a non-canonical pathway of PI3Kγ activation through the interaction of its RA-domain with a putative Ras-like domain (RLD) in alpha subunit of cyclic nucleotide-gated channel (CNGA1) in retinal rod photoreceptors.
The interaction between PI3Kγ and CNGA1 does not appear to play a role in regulation of CNG channel activity, but PI3Kγ uses CNGA1 as an anchoring module to achieve close proximity to its substrate to generate D3-phosphoinositides.
Our studies suggest a functional non-canonical PI3Kγ activation in retinal rod photoreceptor cells.
PMCID: PMC4326362  PMID: 25644171
Cyclic nucleotide-gated channel; Phosphatidylinositol 3-kinase gamma; Photoreceptor outer segments; Ras-associating domain; Ras-like domain
2.  Light Activation of the Insulin Receptor Regulates Mitochondrial Hexokinase. A Possible Mechanism of Retinal Neuroprotection 
Mitochondrion  2013;13(6):10.1016/j.mito.2013.08.005.
The serine/threonine kinase Akt has been shown to mediate the anti-apoptotic activity through hexokinase (HK)-mitochondria interaction. We previously reported that Akt activation in retinal rod photoreceptor cells is mediated through light-dependent insulin receptor (IR)/PI3K pathway. Our data indicate that light-induced activation of IR/PI3K/Akt results in the translocation of HK-II to mitochondria. We also found that PHLPPL, a serine/threonine phosphatase, enhanced the binding of HK-II to mitochondria. We found a mitochondrial targeting signal in PHLPPL and our study suggests that Akt translocation to mitochondria could be mediated through PHLPPL. Our results suggest that light-dependent IR/PI3K/Akt pathway regulates hexokinase-mitochondria interaction in photoreceptors. Down-regulation of IR signaling has been associated with ocular diseases of retinitis pigmentosa, diabetic retinopathy, and Leber Congenital Amaurosis-type 2, and agents that enhance the binding interaction between hexokinase and mitochondria may have therapeutic potential against these ocular diseases.
PMCID: PMC3818532  PMID: 23993956
Insulin receptor; Phosphoinositdie 3-kinase; Glycogen synthase kinase; Insulin; Neuroprotection; Mitochondria; Hexokinase; Akt; Retina; Retinal degenerative diseases; Photoreceptors
3.  Conformation and crystal structures of 1-amino­cyclo­hexa­neacetic acid (β3,3Ac6c) in N-protected derivatives1  
The gauche conformation of backbone torsion angles (ϕ, θ) for β3,-Ac6c-OH is observed in the N-protected derivatives of 1-amino­cyclo­hexa­neacetic acid.
N-Protected derivatives of 1-amino­cyclo­hexa­neacetic acid (β3,3-Ac6c), namely Valeroyl-β3,3-Ac6c-OH [2-(1-pentanamidocyclohexyl)acetic acid, C13H23NO3], (I), Fmoc-β3,3-Ac6c-OH [2-(1-{[(9H-fluoren-9-yloxy)carbonyl]amino}cyclohexyl)acetic acid, C23H25NO4], (II), and Pyr-β3,3-Ac6c-OH {2-[1-(pyrazine-2-amido)cyclohexyl]acetic acid, C13H17N3O3}, (III), were synthesized and their conformational properties were determined by X-ray diffraction analysis. The backbone torsion angles (ϕ, θ) for β3,3-Ac6c-OH are restricted to gauche conformations in all the derivatives, with a chair conformation of the cyclo­hexane ring. In the crystal structure of (I), the packing of mol­ecules shows both carb­oxy­lic acid R 2 2(8) O—H⋯O and centrosymmetric R 2 2(14) N—H⋯O hydrogen-bonding inter­actions, giving rise to chains along the c-axis direction. In (II), centrosymmetric carb­oxy­lic acid R 2 2(8) O—H⋯O dimers are extended through N—H⋯O hydrogen bonds and together with inter-ring π–π inter­actions between Fmoc groups [ring centroid distance = 3.786 (2) Å], generate a layered structure lying parallel to (010). In the case of compound (III), carb­oxy­lic acid O—H⋯Npyrazine hydrogen bonds give rise to zigzag ribbon structures extending along the c-axis direction.
PMCID: PMC4257263  PMID: 25484721
crystal structure; disubstituted-β-amino acids; π–π inter­action; hydrogen bonds; conformation
4.  Crystal structure of (4Z)-1-(3,4-di­chloro­phen­yl)-4-[hy­droxy(4-methyl­phen­yl)methyl­idene]-3-methyl-4,5-di­hydro-1H-pyrazol-5-one 
The title compound, C18H14Cl2N2O2, crystallizes with two mol­ecules, A and B, in the asymmetric unit. In mol­ecule A, the dihedral angles between the central pyrazole ring and pendant di­chloro­benzene and p-tolyl rings are 2.18 (16) and 46.78 (16)°, respectively. In mol­ecule B, the equivalent angles are 27.45 (16) and 40.45 (18)°, respectively. Each mol­ecule features an intra­molecular O—H⋯O hydrogen bond, which closes an S(6) ring and mol­ecule A also features a C—H⋯O inter­action. In the crystal, weak C—H⋯π interactions and aromatic π–π stacking [shortest centroid–centroid separation = 3.707 (2) Å] generate a three-dimensional network.
PMCID: PMC4257223  PMID: 25484715
crystal structure; Schiff-base pyrazole derivative; hydrogen bonding; C—H⋯π inter­actions; aromatic π–π stacking
5.  Crystal structure of 5,5′-[(4-fluoro­phen­yl)methyl­ene]bis­[6-amino-1,3-di­methyl­pyrimidine-2,4(1H,3H)-dione] 
In the title mol­ecule, C19H21FN6O4, the dihedral angles between the benzene ring and essentially planar pyrimidine rings [maximum deviations of 0.036 (2) and 0.056 (2) Å] are 73.32 (7) and 63.81 (8)°. The dihedral angle between the mean planes of the pyrimidine rings is 61.43 (6)°. In the crystal, N—H⋯O hydrogen bonds link mol­ecules, forming a two-dimensional network parallel to (001) and in combination with weak C—H⋯O hydrogen bonds, a three-dimensional network is formed. Weak C—H⋯π inter­actions and π–π inter­actions, with a centroid–centroid distance of 3.599 (2) Å are also observed.
PMCID: PMC4257154  PMID: 25484692
crystal structure; uracil derivatives; biological activity; pyrimidine scaffolds; bis-uracil derivatives
6.  Crystal structure of (Z)-1-(3,4-dichlorophenyl)-3-methyl-4-[(naphthalen-1-yl­amino)(p-tolyl)methylidene]-1H-pyrazol-5(4H)-one 
The title Schiff base compound, C28H21Cl2N3O, was synthesized by the condensation of 1-(3,4-di­chloro­phen­yl)-3-methyl-4-(4-methyl­benzo­yl)-1H-pyrazol-5(4H)-one with 1-aminona­phthalene. The p-tolyl ring is normal to the pyrazole ring, with a dihedral angle of 88.02 (14)°, and inclined to the naphthalene ring system by 78.60 (12)°. The pyrazole ring is inclined to the naphthalene ring system and the di­chloro-substituted benzene ring by 63.30 (12) and 11.03 (13)°, respectively. The amino group and carbonyl oxygen atom are involved in an intra­molecular N—H⋯O hydrogen bond enclosing an S(6) ring motif. There is also a short C—H⋯O contact involving the carbonyl O atom and the adjacent benzene ring. In the crystal, mol­ecules are linked by C—H⋯π inter­actions, forming a three-dimensional structure.
PMCID: PMC4186144  PMID: 25309277
crystal structure; Schiff base; naphthalene; pyrazolone; pyrrole
7.  6-Amino-3-methyl-4-(3,4,5-tri­meth­oxy­phen­yl)-2,4-di­hydro­pyrano[2,3-c]pyrazole-5-carbo­nitrile 
In the title compound, C17H18N4O4, the dihedral angle between the benzene ring and 2,4-di­hydro­pyrano[2,3-c]pyrazole ring system is 89.41 (7)°. The pyran moiety adopts a strongly flattened boat conformation. In the crystal, mol­ecules are linked by N—H⋯N, N—H⋯O, C—H⋯N and C—H⋯O hydrogen bonds into an infinite two-dimensional network parallel to (110). There are π–π inter­actions between the pyrazole rings in neighbouring layers [centroid–centroid distance = 3.621 (1) Å].
PMCID: PMC4158517  PMID: 25249920
crystal structure
8.  Ethyl 6-amino-5-cyano-4-phenyl-2,4-di­hydro­pyrano[2,3-c]pyrazole-3-carboxyl­ate dimethyl sulfoxide monosolvate 
In the asymmetric unit of the title compound, C16H14N4O3·C2H6OS, there are two independent main mol­ecules (A and B) and two dimethyl sulfoxide solvent mol­ecules. In mol­ecule A, the pyran ring is in a flattened sofa conformation, with the sp 3-hydridized C atom forming the flap. In mol­ecule B, the pyran ring is in a flattened boat conformation, with the sp 3-hydridized C atom and the O atom deviating by 0.073 (3) and 0.055 (3) Å, respectively, from the plane of the other four atoms. The mean planes the pyrazole and phenyl rings form dihedral angles of 84.4 (2) and 84.9 (2)°, respectively, for mol­ecules A and B. In the crystal, N—H⋯O and N—H⋯N hydrogen bonds link the components of the structure into chains along [010]. In both solvent mol­ecules, the S atoms are disordered over two sites, with occupancy ratios of 0.679 (4):0.321 (4) and 0.546 (6):0.454 (6).
PMCID: PMC4120557  PMID: 25161577
9.  Draft Genome Sequence of the Field Isolate Brucella melitensis Strain Bm IND1 from India 
Genome Announcements  2014;2(3):e00497-14.
Brucella spp. are facultative intracellular bacterial pathogens causing the zoonotic disease brucellosis. Here, we report the draft genome sequence of the Brucella melitensis strain from India designated Bm IND1, isolated from stomach contents of an aborted goat fetus.
PMCID: PMC4038885  PMID: 24874680
10.  2-[4-(Piperidin-1-yl)-5H-chromeno[2,3-d]pyrimidin-2-yl]phenol 
In the title compound, C22H21N3O2, the pyrimidine ring is essentially planar [maximum deviation = 0.018 (2) Å] and forms dihedral angles of 22.70 (8) and 0.97 (7)°, respectively, with the fused benzene ring and the hy­droxy-substituted benzene ring. The piperidine ring has a chair conformation and the pyran ring has a flattened twist-boat conformation. The hy­droxy group was refined as disordered over two sets of sites in a 0.702 (4):0.298 (4) ratio. The disorder corresponds to a rotation of approxomiately 180° about the C—C bond connecting the phenol group to the pyrimidine ring and hence, both the major and minor components of disorder form intra­molecular O—H⋯N hydrogen bonds. In the crystal, pairs of weak C—H⋯π inter­actions form inversion dimers. In addition, π–π inter­actions are observed between the pyrimidine ring and the hy­droxy-substituted benzene ring [centroid–centroid separation = 3.739 (2) Å].
PMCID: PMC3998607  PMID: 24826150
11.  5-((Meth­oxy­imino)­{2-[(2-methyl­phen­oxy)meth­yl]phen­yl}meth­yl)-N-phenyl-1,3,4-oxa­diazol-2-amine 
In the title mol­ecule, C24H22N4O3, the plane of the oxa­diazole ring forms a dihedral angle of 32.41 (12)° with that of the phenyl ring and dihedral angles of 74.51 (10) and 56.38 (10)° with the planes of the benzene rings. In the crystal, pairs of N—H⋯N hydrogen bonds link molecules into inversion dimers featuring R 2 2(8) graph-set motifs.
PMCID: PMC3998470  PMID: 24765044
12.  4-Cyano-3-fluoro­phenyl 4-(hexa­dec­yl­oxy)benzoate 
In the title compound, C30H40FNO3, the dihedral angle between the benzene rings is 57.76 (7)°. The alkyl chain adopts an all-trans conformation. In the crystal, mol­ecules are linked by pairs of C—H⋯O hydrogen bonds, forming inversion dimers.
PMCID: PMC3998482  PMID: 24764965
13.  Dimethyl 2-[2-(2,4,6-tri­chloro­phen­yl)hydrazin-1-yl­idene]butane­dioate 
In the title compound, C12H11Cl3N2O4, the dihedral angle between the aromatic ring and the hydrazine (NH—N=C) grouping is 52.2 (3)°. The butanedioate groups exhibit planar conformations. An intra­molecular N—H⋯O hydrogen bond links the N—H group of the hydrazine to one of the meth­oxy groups of the butane­dioate moiety. In the crystal, mol­ecules are linked by C—H⋯O hydrogen bonds and π–π inter­actions are also observed [centroid–centroid separation = 3.535 (1) Å].
PMCID: PMC3914063  PMID: 24526964
14.  5-(5′-Fluoro-2′-meth­oxy­biphenyl-3-yl)-1,3,4-oxa­diazol-2-amine 
In the title compound, C15H12FN3O2, the dihedral angles between the central benzene ring and the pendant benzene and oxa­diazole rings are 45.05 (13) and 15.60 (14)°, respectively. The C atom of the meth­oxy group is roughly coplanar with its attached ring [displacement = 0.178 (4) Å]. In the crystal, N—H⋯N hydrogen bonds link the mol­ecules into [010] chains. Weak C—H⋯π inter­actions are also observed.
PMCID: PMC3885053  PMID: 24454229
15.  (Z)-3-Methyl-4-[1-(4-methyl­anilino)propyl­idene]-1-phenyl-1H-pyrazol-5(4H)-one 
In the title mol­ecule, C20H21N3O, the central pyrazole ring forms dihedral angles of 4.75 (9) and 49.11 (9)°, respectively, with the phenyl and methyl-substituted benzene rings. The dihedral angle between the phenyl and benzene rings is 51.76 (8)°. The amino group and carbonyl O atom are involved in an intra­molecular N—H⋯O hydrogen bond. In the crystal, π–π inter­actions are observed between benzene rings [centroid–centroid seperation = 3.892 (2) Å] and pyrazole rings [centroid–centroid seperation = 3.626 (2) Å], forming chains along [111]. The H atoms of the methyl group on the p-tolyl substituent were refined as disordered over two sets of sites in a 0.60 (4):0.40 (4) ratio.
PMCID: PMC3793766  PMID: 24109353
16.  (2Z)-3-(2,4-Di­chloro­phen­yl)-3-hy­droxy-N-phenyl­prop-2-ene­thio­amide 
In the title mol­ecule, C15H11Cl2NOS, the dihedral angle between the phenyl and benzene rings is 72.24 (1)°. In the crystal, pairs of N—H⋯S hydrogen bonds form dimers with twofold rotational symmetry. The dimers are connected by weak C—H⋯O hydrogen bonds, forming a two-dimensional network parallel to (001). An intra­molecular O—H⋯S hydrogen bond is also observed.
PMCID: PMC3770432  PMID: 24046717
17.  2-Benzoyl-4-chloro­phenyl benzoate 
In the title compound, C20H13ClO3, the dihedral angles between the benzoate and the chloro­benzene and benzoyl rings are 68.82 (5) and 53.76 (6)°, respectively, while the dihedral angle between the benzoyl and benzoate rings is 81.17 (5)°. The eight atoms of the benzoyl residue are essentially planar with the exception of the O atom which lies 0.1860 (5) Å out of their mean plane (r.m.s. deviation = 0.97 Å). The nine atoms of benzoate residue are also essentially planar (r.m.s. deviation = 0.20 Å) with the ester O atom showing the greatest deviation [0.407 (12) Å] from their mean plane. In the crystal, mol­ecules are connected into centrosymmetric dimers by pairs of C—H⋯O hydrogen bonds.
PMCID: PMC3685129  PMID: 23795148
18.  2-(1-Amino-4-tert-butyl­cyclo­hex­yl)acetic acid (tBu-β3,3-Ac6c) hemihydrate1  
The title compound, C12H23NO2·0.5H2O, crystallized with two 2-(1-amino-4-tert-butylcyclohexyl)acetic acid mol­ecules, which are present as zwitterions, and one water mol­ecule in the asymmetric unit. The mol­ecular structure of each zwitterion is stabilized by an intra­molecular six-membered (C 6 ) N—H⋯O hydrogen bond. In the crystal, the two independent zwitterions are linked head-to-head by N—H⋯O hydrogen bonds. Further O—H⋯O and N—H⋯O hydrogen bonds link the zwitterions and the water molecules, forming sandwich-like layers, with a hydrophilic filling and a hydrophobic exterior, lying parallel to the ab plane.
PMCID: PMC3685045  PMID: 23795064
19.  TrkB Receptor Signalling: Implications in Neurodegenerative, Psychiatric and Proliferative Disorders 
The Trk family of receptors play a wide variety of roles in physiological and disease processes in both neuronal and non-neuronal tissues. Amongst these the TrkB receptor in particular has attracted major attention due to its critical role in signalling for brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and neurotrophin-4 (NT4). TrkB signalling is indispensable for the survival, development and synaptic plasticity of several subtypes of neurons in the nervous system. Substantial evidence has emerged over the last decade about the involvement of aberrant TrkB signalling and its compromise in various neuropsychiatric and degenerative conditions. Unusual changes in TrkB signalling pathway have also been observed and implicated in a range of cancers. Variations in TrkB pathway have been observed in obesity and hyperphagia related disorders as well. Both BDNF and TrkB have been shown to play critical roles in the survival of retinal ganglion cells in the retina. The ability to specifically modulate TrkB signalling can be critical in various pathological scenarios associated with this pathway. In this review, we discuss the mechanisms underlying TrkB signalling, disease implications and explore plausible ameliorative or preventive approaches.
PMCID: PMC3676832  PMID: 23670594
neurotrophins; neurodegenerative disorders; psychiatric disorders; cancer; retina; glaucoma; TrkB receptor; BDNF; Shp2 phosphatase
20.  3-Methyl-4-{(E)-[4-(methyl­sulfan­yl)benzyl­idene]amino}-1H-1,2,4-triazole-5(4H)-thione 
In the title mol­ecule, C11H12N4S2, the dihedral angle between the triazole and benzene rings is 21.31 (5)°. A weak intra­molecular C—H⋯S hydrogen bond generates an S(6) ring motif. In the crystal, pairs of N—H⋯S hydrogen bonds form inversion dimers. In addition, π–π inter­actions are observed between the benzene rings, with a centroid–centroid separation of 3.7599 (11) Å.
PMCID: PMC3648251  PMID: 23723871
21.  4-Amino-3-(3-meth­oxy­benz­yl)-1H-1,2,4-triazole-5(4H)-thione 
In the title mol­ecule, C10H12N4SO, the triazole ring forms a dihedral angle of 73.0 (5)° with the benzene ring. The meth­oxy group is approximtely coplanar with the benzene ring with a C C—O—Cmeth­yl torsion angle of 4.7 (3)°. In the crystal, N—H⋯S hydrogen bonds connect pairs of inversion-related mol­ecules, which are in turn connected by N—H⋯N hydrogen bonds into chains of rings along [010]. Weak C—H⋯O hydrogen bonds connect these chains into a two-dimensional network parallel to (-102).
PMCID: PMC3648260  PMID: 23723880
22.  (R)-2-Cyano-N-(1-phenyl­eth­yl)acetamide 
In the title compound, C11H12N2O, the dihedral angle between the acetamide group and the benzene ring is 68.7 (1)°. In the crystal, N—H⋯O and weak C—H⋯O hydrogen bonds link the mol­ecules into chains along the a-axis direction.
PMCID: PMC3647851  PMID: 23723817
23.  Ethyl 2-(quinolin-8-yl­oxy)acetate monohydrate 
In the title compound, C13H13NO3·H2O, the dihedral angle between the ethyl ester group [C—C—O—C(=O); maximum deviation = 0.003 (2) Å] and the quinoline ring system is 7.94 (12)°. The water solvent mol­ecule is linked to the title mol­ecule via O—H⋯O and O—H⋯N hydrogen bonds. In the crystal, mol­ecules are linked by C—H⋯O hydrogen bonds, forming chains propagating along [100].
PMCID: PMC3629657  PMID: 23634144
24.  5-Bromo-2-chloro­pyrimidin-4-amine 
In the title compound, C4H3BrClN3, the pyrimidine ring is essentially planar (r.m.s. deviation from the plane = 0.087 Å). In the crystal, pairs of N—H⋯N hydrogen bonds connect the mol­ecules into inversion dimers; these are connected by further N—H⋯N hydrogen bonds into a two-dimensional framework parallel to the bc plane.
PMCID: PMC3629628  PMID: 23634115
25.  Ethyl 2,6-bis­(4-chloro­phen­yl)-4-(4-fluoro­anilino)-1-(4-fluoro­phen­yl)-1,2,5,6-tetra­hydro­pyridine-3-carboxyl­ate 
In the title compound, C32H26Cl2F2N2O2, the tetra­hydro­pyridine ring adopts a distorted boat conformation. The chlorophenyl rings are inclined to one another by 55.2 (1)°, while for the fluorophenyl rings the dihedral angle is 80.7 (1)°. The amino group and carbonyl O atom are involved in an intra­molecular N—H⋯O hydrogen bond. In the crystal, weak C—H⋯O, C—H⋯F and C—H⋯Cl inter­actions link the mol­ecules into a three-dimensional network.
PMCID: PMC3629536  PMID: 23634054

Results 1-25 (93)