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Chemo-, regio-, and stereoselective Heck–Matsuda arylation of allylic alcohols under mild conditions
No full textHeck arylation with allylic alcohol is extremely challenging due to chemo-, regio-, and stereoselective scrambling. Here we report a mild protocol for the alcohol selective β- and α-arylation of allylic and cinnamyl alcohols respectively with aryldiazonium salts. The steric and electronic parameters of the alkene play a prominent
role in the regioselectivit
Synergistic actions of melatonin in combination with anti-parkinsonian drugs in experimental model of Parkinson’s disease
No full textParkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive
degeneration and loss of nigrostriatal dopaminergic neurons in the midbrain, A9
substantia nigra neurons leading to severe striatal dopamine (DA) depletion resulting in
tremor, rigidity and hypokinesia (Carlsson, 2002). PD is named after James Parkinson
who first described the disease as “Shaking Palsy” (Paralysis Agitans) in his classic
monograph “An essay on the Shaking Palsy” (Parkinson, 1817). This debilitating disorder
has no cure existing, and recent epidemiological studies suggest an increasing trend in
its incidents; predicting an alarming 2-fold increase in affected population by 2030 in
several countries (Dorsey et al., 2007).
Currently used drugs for PD provides symptomatic relief, and are based on increasing
the striatal levels of DA, or controlling the DA transmission. However, these drugs are
generally short acting, and with time develop serious side effects. There are cases when
the drugs need to be discontinued due to exacerbation of DA-mediated effects. At this
juncture, there is a great need of alternative therapies, or designs that would effectively
reduce the dose of drugs that causes ‘on-off’ effects, dyskinesias, other undesirable
motor effects, non-motor complications, and slower the progression of the disease.
One of such effective therapy is using a peripheral aromatic amino acid decarboxylase
inhibitor, carbidopa along with L-3,4-dihydroxyphenylalanine (L-DOPA). The present
study mainly addressed such alternative approaches so as to find better therapeutic
agents that may synergize with the existing PD drugs
A Rapid One-Pot Ugi Reaction Based Route to Novel Imidazole-Fused Benzodiazepinones
No full textA short and efficient synthetic approach has been developed for the synthesis of a variety of imidazole-fused benzodiazepinones. It is based on a Ugi multicomponent reaction strategy and uses various isocyanides to generate the key intermediates for a Mumm rearrangement process. The method is suitable for rapid syntheses of fused azaheterocycles of pharmacological interes
Synthetic Studies on Fused N-/O-Based Heterocycles and Sugar Containing Heterocyclic Molecules of Biological Importance
No full textChapter I. This chapter is sub-divided into 4 parts.
Part A contains a brief review of the metal mediated coupling reactions for the synthesis of N-/O-rich heterocycles mainly by Sonogashira cyclization reactions. The recent modifications of Sonogashira cyclization reactions are also included in this part.
Part B. In this section green approach for the regio- & stereo-selective syntheses of Z)-3-methyleneisoindoline-1-ones in aqueous medium has been described. The introduction to the work, results and discussion, experimental procedures, conclusion, spectroscopic data and related references are also included. The work has been published
in Tetrahedron Lett. 2013, 54, 3748-3751.
Part C contains the synthesis of 3-alkyl/aryl-3-(pyrrole-2-yl)-2-phenyl-2,3-dihydroisoindolinones and 3-alkyl/aryl-3-(indole-3-yl)-2-phenyl-2,3-dihydro-isoindolinones using
nanodomain cubic cuprous oxide as reusable catalyst in aqueous medium under one-pot condition. The introduction to the work, results and discussion, experimental procedures,
conclusion, spectroscopic data and related references are included. The work has been published in RSC Adv., 2014, 4, 7024-7029.
Part D deals with regio- and stereo- selective syntheses of (Z)-3-methyleneisoindoline- 1-ones and furo[3,2-h]quinolines using reusable palladium nanoparticles in onepot domino Sonogashira-cyclization in aqueous medium. The introduction, results and discussion, experimental procedures, conclusion, spectroscopic data and related references are included. The work has been communicated to Tetrahedron Lett.
Chapter II. This chapter is sub-divided into three parts.
Part A. This part contains a brief review of the syntheses of 1,2,3-triazole linked
glycoconjugates and fused heterocycles. The syntheses of some important biologically active compounds along with related references reported in the literature are also
incorporated.
Part B. Application of nanodomain cubic cuprous oxide as reusable catalyst for the synthesis of triazole-fused tetracyclic glycosides and heterocycles in aqueous medium is
described in this chapter. The introduction to the work, results and discussion, experimental procedures, conclusion, spectroscopic data and related references are included. The work has been published in Tetrahedron Lett. 2015, 56, 3886-3889.
Part C deals with the syntheses of triazolo benzoxazines, triazolo quinoxalines,
triazolo benzodiazepines, triazolo benzoxazepines and triazolo benzthiazines via a simple and convenient protocol using basic alumina as solid support. The introduction to the work, results and discussion, experimental procedures, conclusion, spectroscopic data and related references are included in this part. The work has been published in Tetrahedron Lett. 2014, 55, 2261-2265
A comparative study on the interaction of the putative anticancer alkaloids, sanguinarine and chelerythrine, with single- and double-stranded, and heat-denatured DNAs
No full textA detailed investigation on the interaction of two benzophenanthridine alkaloids, sanguinarine (SGR) and chelerythrine (CHL), with the double-stranded (ds), heat-denatured (hd), and single-stranded (ss) DNA was performed by spectroscopy and calorimetry techniques. Binding to the three DNA conformations leads to quenching of fluorescence of SGR and enhancement in the fluorescence of CHL. The binding was cooperative for both of the alkaloids with all the three DNA conformations. The binding constant values of both alkaloids with the ds DNA were in the order of 106 M−1; binding was weak with hd and much weaker to the ss DNA. The fluorescence emission of the alkaloid molecules bound to the ds and hd DNAs was quenched much less compared to those bound to the ss DNA based on competition with the
anionic quencher KI. For both double stranded and heat denatured structures the emission of the bound alkaloid
molecules was polarized significantly and strong energy transfer from the DNA bases to the alkaloid molecules occurred. Intercalation of SGR and CHL to ds, hd, and ss DNA was proved from these fluorescence results. Calorimetric studies suggested that the binding to all DNA conformations was both enthalpy and entropy favored. Both the alkaloids preferred double-helical regions for binding, but SGR was a stronger binder than CHL to all the three DNA structures
Extreme multistability: Attractor manipulation and robustness
No full textThe coexistence of infinitely many attractors is called extreme multistability in dynamical systems.
In coupled systems, this phenomenon is closely related to partial synchrony and characterized by the
emergence of a conserved quantity. We propose a general design of coupling that leads to partial
synchronization, which may be a partial complete synchronization or partial antisynchronization and
even a mixed state of complete synchronization and antisynchronization in two coupled systems and, thereby reveal the emergence of extreme multistability. The proposed design of coupling has wider options and allows amplification or attenuation of the amplitude of the attractors whenever it is necessary. We demonstrate that this phenomenon is robust to parameter mismatch of the coupled oscillators
Stepwise Unfolding of Bovine and Human Serum Albumin by an Anionic Surfactant: An Investigation Using the Proton Transfer Probe Norharmane
No full textInteractions of the anionic surfactant sodium dodecyl sulfate (SDS) with thetransport proteins bovine serum albumin (BSA) and human serum albumin (HSA) have
been divulged using an external photoinduced proton transfer probe, norharmane (NHM).Steady-state fluorometry, time-resolved measurements, micropolarity analysis, circular
dichroism (CD), and isothermal titration calorimetry (ITC) have been exploited for the study. With the gradual addition of SDS to the probe-bound proteins, the fluorometric responses of the different prototropic species of NHM exhibit an opposite pattern as to that observed while NHM binds to the proteins. The study reveals a sequential unfolding of the serum proteins with the gradual addition of SDS. ITC measures the heat changes associated
with each step of the unfolding. ITC experiments, carried out at two different pH’s, elucidate the nature of interaction between SDS and the two serum proteins. At a very high concentration of SDS, the external probe (NHM) is found to be dislodged from the protein environments to bind to the SDS micellar medium
Identification of important interacting proteins (IIPs) in Plasmodium falciparum using large-scale interaction network analysis and in-silico knock-out studies
No full textBackground: Plasmodium falciparum causes the most severe form of malaria and affects 3.2 million people annually.
Due to the increasing incidence of resistance to existing drugs, there is a growing need to discover new and more
effective drugs against malaria. Despite the global importance of P. falciparum, vast majority of its proteins are uncharacterized experimentally. Application of newer approaches using several “omics” data has become successful for exploring the biological interactions underlying cellular processes. Till date not many system level study has been published using P. falciparum protein protein interaction. Hence, the purpose of this study is to develop a standardized pipeline for structural, functional, and topographical analysis of large scale protein protein interaction network (PPIN) in
order to identify proteins important for network topology and integrity. Here, P. falciparum PPIN has been utilized as a model for better understanding of the molecular mechanisms of survival and pathogenesis of malaria parasite.
Methods: Various graph theoretical approaches were implemented to identify highly interacting hub and central
proteins that are crucial for network integrity. Further, potential network perturbing proteins via an in-silico knock-out (KO) analysis to isolate important interacting proteins (IIPs), which in principle, can elicit significant impact on the global and local environments of the P. falciparum interaction network.
Results: 177 hubs and 132 central proteins were identified from the malarial (proteins: 1607; interactions: 4750) PPI
networks. Using the in-silico knock-out exercise 131 and 99 global and local network perturbing proteins were also
identified. Finally, 271 proteins from P. falciparum were shortlisted as important interacting proteins (IIPs), which not only play crucial role in intra-pathogen network integrity, stage specificity but also interact with various human proteins involved in multiple metabolic pathways within the host cell. These IIPs could be used as potential drug targets in malarial research.
Conclusion: Graph theoretical analysis of PPIN can be a very useful approach to identify proteins that are important
for regulation of the interactions required for an organism’s survival. Important interacting proteins (IIPs) identified using P. falciparum PPIN provides a useful dataset containing probable candidates for future drug target analysis
pH-induced structural change of a multitryptophan protein MPT63 with immunoglobulinlike fold: identification of perturbed tryptophan residue/residues
No full textThe structural change of M. tuberculosis MPT63, which is predominantly a β-sheet protein having an immunoglobulin
like fold, has been investigated in the pH range 7.5–1.5 using various biophysical techniques along with low-temperature phosphorescence (LTP) spectroscopy. MPT63 contains four Tryptophan (Trp) residues at 26, 48, 82, and 129. Although circular dichroism, steady-state and time-resolved fluorescence, time-resolved anisotropy, 1-aniline-8-naphthalene sulfonic(ANS) acid binding, and analytical ultracentrifuge depict more open largely unfolded structure of MPT63 at pH 1.5 and also more accessible nature of Trp residues to neutral quencher at pH 1.5, it is, however, not possible to assign the specific Trp residue/residues being perturbed. This problem has been resolved using LTP of MPT63, which shows optically resolved four distinct (0, 0) bands corresponding to four Trp residues in the pH range 7.5–3.0. LTP at pH 1.5 clearly reveals that the solvent-exposed Trp 82 and the almost buried Trp 129 are specifically affected compared with Trp 48 and Trp 26. Lys 8 and Lys 27 are predicted to affect Trp 129. Tyrosine residues are found to be silent even at pH 1.5.This type of specific perturbation in a multi-Trp protein has not been addressed before. LTP further indicates that partially
exposed Trp 48 is preferentially quenched by acrylamide compared with other Trp residues at both pH 7.5 and
1.5. The solvent-exposed Trp 82 is surprisingly found to be not quenched by acrylamide at pH 7.5. All the results are
obtained using micromolar concentration of protein and without using any Trp-substituted mutan
Eukaryotic tRNAs fingerprint invertebrates vis-àvis vertebrates
No full textDuring translation, aminoacyl-tRNA synthetases recognize the identities of the tRNAs to charge them with their respective amino acids. The conserved identities of 58,244 eukaryotic tRNAs of 24 invertebrates and 45 vertebrates in genomic tRNA database were analyzed and their novel features extracted. The internal promoter sequences, namely, A-Box and B-Box, were investigated and evidence gathered that the intervention of optional nucleotides at 17a and 17b correlated with the optimal length of the A-Box. The presence of canonical transcription terminator sequences at the immediate vicinity of tRNA genes was ventured. Even though non-canonical introns had been reported in red alga, green alga, and nucleomorph so far, fairly motivating evidence of their existence emerged in tRNA genes of other eukaryotes. Noncanonical introns were seen to interfere with the internal promoters in two cases, questioning their transcription fidelity. In a first of its kind, phylogenetic constructs based on tRNA molecules delineated and built the trees of the vast and diverse invertebrates and vertebrates. Finally, two tRNA models representing the invertebrates and the vertebrates were
drawn, by isolating the dominant consensus in the positional fluctuations of nucleotide composition