2058 research outputs found
Sort by
ZnI2‑Catalyzed Diastereoselective [4 + 2] Cycloadditions of β,γ‑Unsaturated α‑Ketothioesters with Olefins
No full textThe potential of β,γ-unsaturated α-ketothioesters participating in hetero-Diels−Alder reaction has remained
unexplored. We report herein the first study of a ZnI2-catalyzed highly diastereoselective inverse electron demand hetero-Diels−Alder reaction of β,γ-unsaturated α-ketothioesters with olefins to access highly substituted 3,4-dihydro-2H-pyrans. All the reactions proceed with cis-selectivity in moderate to excellent yields. Under similar reaction conditions, terminal alkynes undergo direct conjugate 1,4-addition to yield δ,ε-acetylenic α-ketothioesters. Furthermore, the utility of these cycloadducts has been demonstrated by an NBS-MeOH mediated stereospecific efficient access to fully substituted pyran rings. The product bromoethers undergo E2 elimination with DBU, resulting in substituted 3,6-dihydro-2H-pyrans. In addition, the thioester moiety of the products has been used for further transformations, such as amidations and Fukuyama coupling reactions
Melatonin enhances L-DOPA therapeutic effects, helps to reduce its dose, and protects dopaminergic neurons in 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice
No full textL-3,4-dihydroxyphenylalanine (L-DOPA) reduces symptoms of
Parkinson’s disease (PD), but suffers from serious side effects on long-term use.
Melatonin (10–30 mg/kg, 6 doses at 10 hr intervals) was investigated to
potentiate L-DOPA therapeutic effects in 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP)-induced parkinsonism in mice. Striatal tyrosine
hydroxylase (TH) immunoreactivity, TH, and phosphorylated ser 40 TH
(p-TH) protein levels were assayed on 7th day. Nigral TH-positive neurons
stereology was conducted on serial sections 2.8 mm from bregma rostrally to
3.74 mm caudally. MPTP caused 39% and 58% decrease, respectively, in
striatal fibers and TH protein levels, but 2.5-fold increase in p-TH levels. About
35% TH neurons were lost between 360 and 600 lm from 940 lm of the entire
nigra analyzed, but no neurons were lost between 250 lm rostrally and 220 lm
caudally. When L-DOPA in small doses (5–8 mg/kg) failed to affect MPTPinduced
akinesia or catalepsy, co-administration of melatonin with L-DOPA
attenuated these behaviors. Melatonin administration significantly attenuated
MPTP-induced loss in striatal TH fibers (82%), TH (62%) and p-TH protein
(100%) levels, and nigral neurons (87–100%). Melatonin failed to attenuate
MPTP-induced striatal dopamine depletion. L-DOPA administration (5 mg/kg,
once 40 min prior to sacrifice, p.o.) in MPTP- and melatonin-treated mice
caused significant increase in striatal dopamine (31%), as compared to
L-DOPA and MPTP-treated mice. This was equivalent to 8 mg/kg L-DOPA
administration in parkinsonian mouse. Therefore, prolonged, effective use of
L-DOPA in PD with lesser side effects could be achieved by treating with 60%
lower doses of L-DOPA along with melatonin
Bioactive Peptides and Enzymes : Their Stability, Assembly and Function
No full textProteases probably arose at the earliest stages of protein evolution as simple destructive enzymes which were necessary for protein catabolism and generation of amino acids in primitive organisms. Proteolysis of peptide bonds is one of the most important enzymatic modification of proteins. In the earlier days, proteolysis was always associated with protein digestion involving digestive proteases of pancreatic and gastric origin but the interest in study of proteases was stimulated by the recognition that they are involved in the regulation of a number of physiological processes. One of these functions involves zymogen activation by‘limited proteolysis’. Certain proteins are synthesized as inactive precursors or zymogens and selective enzymatic cleavage of peptide bonds converts them into the physiologically active form (Figure 2). This is involved in various biological processes like blood coagulation, fibrinolysis, complement reaction, hormone production, development, differentiation, supramolecular assembly etc. All of these involve zymogen activation in one or more steps (Neurath 1976; Dawie and Fujikawa, 1975; Cabib and Farkas, 1971). The specificity of limited
proteolysis is best understood in terms of the three-dimensional structure of a protein substrate and of the attacking protease because the region of the protein substrate containing the susceptible peptide bond must fit the active site of the attacking protease in order for amino
acid residues of the substrate to interact with primary as well as secondary binding sites of the enzym
Chelerythrine–lysozyme interaction: spectroscopic studies, thermodynamics and molecular modeling exploration
No full textThe binding of the iminium and alkanolamine forms of chelerythrine to lysozyme (Lyz) was investigated by spectroscopy and docking studies. The thermodynamics of the binding was studied by calorimetry. Spectroscopic evidence suggested that Trp-62 and Trp-63 in the b-domain of the protein are closer to the binding site; moreover, the binding site was at a distance of 2.27 and 2.00 nm from the iminium and alkanolamine forms, respectively, according to the Forster theory of non-radiation energy transfer. The
equilibrium binding constants for the iminium and alkanolamine forms at 298 K were evaluated to be 1.29 � 105 and 7.79 � 105 M�1, respectively. The binding resulted in an alteration of the secondary structure of the protein with a distinct reduction of the helical organization. The binding of iminium was endothermic, involving electrostatic and hydrophobic interactions, while that of alkanolamine form was exothermic and dominated by hydrogen bonding interactions. Docking studies provided the atomistic
details pertaining to the binding of both forms of chelerythrine and supported the higher binding in
favour of the alkanolamine over the iminium. Furthermore, molecular dynamics study provided accurate insights regarding the binding of both chelerythrine forms in accordance with the experimental results obtained. Chelerythrine binding pocket involves the catalytic region and aggregation prone K-peptide region, which are sandwiched between one another. Overall, these results suggest that both the forms of the alkaloid bind to the protein but the neutral form has higher affinity than the cationic form
Design and Synthesis of Triazole based Peptidomimetic Macrocycles and other Heterocycles: Studies on the Self-Assembly and Anion Binding Property of the Macrocycles
No full textdescribes a literature review on several classes of cyclic peptide nanotubes based on cyclic D-,L-,α-peptides, cyclic D-,L-,α,γ peptides and also cyclic-β-peptides. It is focused
on macrodipole modification of cyclic peptides by substituting an amide functional group with a perfect mimic of peptide bond to access more effective artificial ion channels. The major point that came out in this regard was that (1,4)-linked triazole shares a number of features with peptide bond in terms of bond-distance, planarity, H-bond accepting as well as donating ability. This review also contains a short discussion of the basic information about
the advantage of D-glucose derived cis-β-furanoid sugar moiety which has desired structural features to allow the product to attain a conformation conducive for self assembly. The second part of this chapter describes the construction of two types of novel heterocyclic
backbone modified macrocyclic peptides by incorporation of an α-amino acid/β-amino acid with cis-β-furanoid (1,4)-linked triazole amino acid. The macrocyclic peptides featuring α- amino acids are able to maintain pseudo cyclo-β-peptide conformation, while that based on β- amino acid forms only a conformationally homogeneous cyclic peptide. One of the cyclic peptides is able to undergo parallel homo-stacking via amide NH and amide carbonyl oxygen H-bonding like cyclo-β-peptides
Study of molecular recognition using designed ligands
No full textMolecular recognition is the pillar on which complex biological systems stand. The basic
biological processes, like transcription, translation, metabolism, cellular signaling etc.,
mainly involve molecular interactions, e.g. protein-protein, protein-DNA or protein-small
molecule interactions. In this work, an attempt has been made to recognize different effects of
nature of interaction on transcription and cellular signaling process
PPh3·HBr−DMSO: A Reagent System for Diverse Chemoselective Transformations
No full textThe broad applicability of the hitherto unexplored
reagent combination PPh3·HBr−DMSO is exemplified with multiplehighly diverse one-step transformations to synthetically useful building blocks, such as flavones, 4H-thiochromen-4-ones, α-hydroxy ketones,1,4-naphthoquinones (including vitamin K3), 2-bromo-3-substituted- 1H-1-indenones, 2-methylthio-1H-1-indenonesbutyne-1 ,2-dione,and 4-pentene-2,3-diones. The simple and mild reaction conditions make the reagent superior in terms of yield and substrate scope in comparison with the existing alternative
Tricarbonyl 99mTc(I) and Re(I)–thiosemicarbazone complexes: synthesis, characterization and biological evaluation for targeting bacterial infection
No full textMethyl, ethyl and phenyl nitrofuryl thiosemicarbazone ligands (1, 2 and 3 respectively) were radiolabeled
with freshly prepared aqueous solution of a fac[99mTc(CO)3(H2O)3]+ precursor. The radiochemical yield was around 98% as determined by thin layer chromatography and HPLC. The complexes exhibited substantial stability. The corresponding Re(I) complexes were prepared from a Re(CO)5Br precursor to understand the coordination behavior of the ligands against a tricarbonyl rhenium(I) precursor. The rhenium(I) complexes were characterized by means of IR, NMR and mass spectroscopic studies as well as by X-ray
crystallography, and correlated with the technetium complexes by means of HPLC studies. Electrochemical
reduction of monomeric Re(CO)3-complexes of nitrofuryl ethyl thiosemicarbazone was also studied using cyclic voltammetry. Biodistribution studies of 99mTc(CO)3-labeled thiosemicarbazones in rats intramuscularly infected with S. aureus exhibited substantial in vivo stability of the complex and moderate accumulation at the site of focal infectio
ARSENIC INDUCED HEALTH EFFECTS, GENETIC SUSCEPTIBILITY AND THE ROLE OF BACTERIA IN GROUND WATER ARSENIC CONTAMINATION
No full textMore than 150 million people throughout the world are exposed to arsenic through either drinking water or other sources. It is an exclusive human carcinogen and has no carcinogenic effect on other animals. Six states of India are majorly contaminated by this deadly toxin. In West Bengal, ground water of 9 out of 16 districts are contaminated with arsenic and over 26 million individuals are at health risk. The arsenic-induced adverse health effects, genetic damage and susceptibility to arsenicosis were evaluated in this dissertation. Attempts have also been made to evaluate the seasonal variations in the ground water arsenic contamination in different parts of India and the role of bacteria in ground water arsenic contamination. We selected individuals from Murshidabad district of West Bengal as our arsenic exposed population, where water analysis showed significantly high levels of arsenic concentrations than the maximum permissible limit of 10μg/L as set by World Health Organization (WHO) and United States Environmental Protection Agency (USEPA). Individuals from East Midnapur district was selected as our control population since there is no arsenic contamination in their drinking water. For the investigation of seasonal changes of ground water arsenic content and the role of bacteria in arsenic contamination of drinking water, samples were collected from four highly contaminated regions of India along the Ganga-Brahmaputra-Barak basin (Nadia and Murshidabad districts of the lower Ganga fluvial plains, Ara district of the middle Ganga plain, and the Cachar district of Brahmaputra-Barak plain).
Epidemiological studies show a wide range of adverse health disorders including skin pigmentations, keratosis, peripheral neuropathy, conjunctivitis, respiratory diseases, liver and cardiovascular problems along with cancers of skin and different internal organs. Although a large number of individuals are exposed to arsenic through drinking water but only about 10-15% exposed individuals showed arsenic induced skin lesions which suggests that susceptibility to arsenic is distinctly different among individuals. Thus, the exposed study group was divided into two broad categories - individuals manifesting the characteristic arsenic induced skin lesions (symptomatic) and those who do not develop them (asymptomatic). To further explore the impact of arsenic exposure on health status, we examined the prevalence of three most frequently encountered disorders like peripheral neuropathy, respiratory illness band eye problems within the arsenic exposed population (with and without skin lesions) and compared with the control group. The risk of developing liver and cardiovascular diseases on exposure to arsenic was also investigated. Arsenic induced cytogenetic damage was assessed along with genetic variants that may have an association with arsenic susceptibility.
A total of 535 arsenic-exposed individuals (277 with skin lesions and 258 without skin lesions) and 107 arsenic unexposed participants were recruited for our study. It was observed that peripheral neuropathy, respiratory diseases and eye problems are prevalent at a significantly higher rate in individuals exposed to arsenic compared to the unexposed group. Exposed individuals with skin lesions had much higher occurrence of all three diseases, indicating that people who are highly susceptible to arsenic toxicity are also more likely to develop these non-dermatological health problems.
Towards the aim of predicting the extent of liver and cardiovascular disease risk in the arsenic exposed population, we assessed bioindicators of hepatocellular injury as indicated by the serum levels of liver enzymes, determined the autoimmune status as indicated by the amounts of serum ANA and anti-dsDNA and measured circulating inflammatory cytokines related to cardiovascular diseases. The results were compared with levels of these parameters in the arsenic unexposed group. Various tests are performed to detect specific liver activities ensuing proper functioning of the liver. Among all parameters, serum bilirubin is the indicator that marks liver’s capacity of organic anion transport and drug metabolism, while aminotransferase (ALT, AST), alkaline phosphatase (ALP) and aminopeptidase levels suggest injury to hepatocytes. Elevated or abnormal levels of these liver function test parameters in an individual indicate underlying liver diseases. In our study we have found significantly increased serum levels of bilirubin, ALT, AST, and ALP in the arsenic exposed population compared to unexposed individuals.
Cytokines play key roles in systemic inflammation leading to cardiovascular diseases. We observed significantly increased circulating levels of cardiovascular disease associated inflammatory cytokines IL6 and IL8 in the arsenic exposed population compared to the control. We have also found a significant increase in the serum levels of autoimmune biomarkers antinuclear antibody (ANA) and anti-double stranded DNA (anti-dsDNA) in arsenic exposed population, indicating that arsenic exposure also induces autoimmune diseases. Both autoimmune and liver diseases are risk factors for cardiovascular ailments. Thus, the arsenic exposure induced hepatic injury and systemic inflammatory diseases most likely contributes to the increased cardiovascular disease risk observed in our arsenic exposed populations (Das et. al., 2012)
Chemical Transformation and Biological Evaluation of Different Bioactive Constituents Isolated from Andrographis paniculata and Chenopodium album
No full textPlants have traditionally served as man’s most important weapon against pathogen. Traditional medicine has been defined as the sum of the knowledge, skills and practices based on the theories, beliefs and experiences indigenous to different culture, whether explicable or not, used in the maintenance of health as well in the prevention, diagnosis, improvement or treatment of physical and mental illness [1]. In many developing countries, a large part of the population, especially in rural areas, depend mainly on traditional medicine for their primary
health care. Medicinal plants are widely used by all sections of community; whether directly as folk remedies or the medicaments of the different indigenous system as well as in modern medicine [2, 3] India has been identified as a major resourceful area in the traditional and alternative medicines globally. Medicinal plants constitute an important component of flora
and are wildly distributed in India. Andrographis paniculata (Burm. f.) Nees is one of the
wildly distributed medicinal plants in India and using since ancient times in traditional ayurvedic systems of medicines. It can be found in a variety of habitats, e.g plains, hill slopes, wastelands, farms, dry or wet lands, sea sore and even in road sides. It is available abundantly in south eastern Asia, i.e., India, Sri Lanka, Pakistan and Indonesia. It is found in wild
through out of plains of India especially in West Bengal, Tamil Nadu, Karnataka, Maharashtra, Orissa, Uttar Pradesh and Uttarakhand. Andrographis peniculata, Kalmegh, of Ayurveda is an erect annual herb extremely bitter in taste in each and every part of the plant body. The plant is known in north-eastern India as ‘Maha-tita’, literally ‘King of bitters’ and also known by various other vernacular names. It is also known as ‘Bhui-neem’ since theplant, though much smaller in size and has bitter taste as that of Neem (Azadirachta indica)