01644nas a2200193 4500008004100000022001400041245011800055210006900173260007100242300001400313490000700327520087900334100001701213700002001230700002501250700002901275700001801304856012801322 2009 eng d a0888-588500aMass transfer and solubility of CO and H-2 in ionic liquid. case of [Bmim][PF6] with gas-inducing stirrer reactor0 aMass transfer and solubility of CO and H2 in ionic liquid case o a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcAPR a4075-40820 v483 a

Since the past decade, ionic liquids have gained significant importance as alternative solvents for catalysis applications. Many of the reactions evaluated in ionic liquids employ gases as substrates, and therefore it is important to know their solubility and mass transfer characteristics. This work reports for the first time both the solubility and volumetric gas-liquid mass transfer coefficient k(La) for hydrogen and carbon monoxide in 1-n-butyl-3-methylimidazolium hexafluorophosphate ([Bmim][PF6]) at three temperatures (293, 323, and 373 K) in relevance to hydroformylation reaction. The experimental data on the volumetric gas-liquid mass transfer coefficient are described by a dimensionless correlation for the bench-scale stirred tanks with gas-inducing impeller. k(La) values have also been evaluated for different [Bmim][PF6]-decane emulsions at 373 K.

1 aSharma, Amit1 aJulcour, Carine1 aKelkar, Ashutosh, A.1 aDeshpande, Raj, Madhukar1 aDelmas, Henri uhttps://library.ncl.res.in/content/mass-transfer-and-solubility-co-and-h-2-ionic-liquid-case-bmimpf6-gas-inducing-stirrer-001537nas a2200193 4500008004100000022001400041245014600055210006900201260007100270300001600341490000700357520072900364100001701093700002901110700002901139700002501168700001801193856013201211 2010 eng d a0888-588500aHydroformylation of 1-octene using [Bmim][PF6]-decane biphasic media and rhodium complex catalyst: thermodynamic properties and kinetic study0 aHydroformylation of 1octene using BmimPF6decane biphasic media a a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcNOV a10698-107060 v493 a

A chemical reaction engineering approach is reported to investigate the biphasic hydroformylation of I-octene using [bmim][PF6] ionic liquid. It is based both on a process parameter investigation (temperature, concentrations, and pressures) and a thermodynamic study of the reaction medium (gas liquid and liquid liquid equilibria). Initial rate data show complex behavior with respect to operating parameters and are best described by a rate equation based on a mechanistic model. Complete reaction scheme including isomerization is then modeled accounting from the time dependent concentration of the organic substrates measured in organic phase and recalculated in ionic liquid phase from liquid liquid equilibria.

1 aSharma, Amit1 aLebigue, Carine, Julcour1 aDeshpande, Raj, Madhukar1 aKelkar, Ashutosh, A.1 aDelmas, Henri uhttps://library.ncl.res.in/content/hydroformylation-1-octene-using-bmimpf6-decane-biphasic-media-and-rhodium-complex-catalyst-001671nas a2200289 4500008004100000022001400041245015900055210006900214260007300283300001200356490001000368520061900378653002100997653002001018653002001038653001601058653001901074100002301093700002001116700001701136700002501153700001701178700001801195700001801213700001801231856013201249 2013 eng d a0169-131700aUltrasound promoted efficient and green protocol for the expeditious synthesis of 1, 4 disubstituted 1, 2, 3-triazoles using Cu(II) doped clay as catalyst0 aUltrasound promoted efficient and green protocol for the expedit aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcAUG a351-3570 v80-813 a

Cu(II) doped clay catalyst has been prepared by an easy technique from inexpensive starting materials and investigated for the one pot synthesis of 1, 4-disubstituted 1, 2, 3-triazoles via Huisgen [3 + 2] cycloaddition under ultrasonic irradiation at room temperature. The catalyst is highly active, selective, and stable and can be reused several times. The prepared catalyst has been characterized by XRD, BET-SA, H-2-TPR, SEM and XPS techniques. This transformation is fast, efficient and does not require nitrogen atmosphere or anoxic conditions and additive. (C) 2013 Elsevier B.V. All rights reserved.

10aCatalyst support10aCopper catalyst10aCrystallization10aselectivity10aSustainability1 aDar, Bashir, Ahmad1 aBhowmik, Amrita1 aSharma, Amit1 aSharma, Parduman, R.1 aLazar, Anish1 aSingh, A., P.1 aSharma, Meena1 aSingh, Baldev uhttps://library.ncl.res.in/content/ultrasound-promoted-efficient-and-green-protocol-expeditious-synthesis-1-4-disubstituted-1-001881nas a2200265 4500008004100000022001400041245011900055210006900174260000800243300001400251490000700265520098400272100001601256700001801272700002001290700002101310700002601331700002401357700002801381700001701409700002201426700001701448700002101465856012901486 2018 eng d a0022-262300aSpecific stereoisomeric conformations determine the drug potency of cladosporin scaffold against malarial parasite0 aSpecific stereoisomeric conformations determine the drug potency cJUL a5664-56780 v613 a

The dependence of drug potency on diastereomeric configurations is a key facet. Using a novel general divergent synthetic route for a three-chiral center antimalarial natural product cladosporin, we built its complete library of stereoisomers (cladologs) and assessed their inhibitory potential using parasite-, enzyme-, and structure-based assays. We show that potency is manifest via tetrahyropyran ring conformations that are housed in the ribose binding pocket of parasite lysyl tRNA synthetase (KRS). Strikingly, drug potency between top and worst enantiomers varied 500-fold, and structures of KRS-cladolog complexes reveal that alterations at C3 and C10 are detrimental to drug potency whereas changes at C3 are sensed by rotameric flipping of glutamate 332. Given that scores of antimalarial and anti-infective drugs contain chiral centers, this work provides a new foundation for focusing on inhibitor stereochemistry as a facet of antimicrobial drug development.

1 aDas, Pronay1 aBabbar, Palak1 aMalhotra, Nipun1 aSharma, Manmohan1 aJachak, Goraknath, R.1 aGonnade, Rajesh, G.1 aShanmugam, Dhanasekaran1 aHarlos, Karl1 aYogavel, Manickam1 aSharma, Amit1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/specific-stereoisomeric-conformations-determine-drug-potency-cladosporin-scaffold-against04015nas a2200217 4500008004100000245010000041210006900141260000800210300001600218490000600234520328400240100001803524700001603542700002203558700001703580700001703597700001803614700001703632700002103649856012703670 2021 eng d00aDesign, synthesis, and structural analysis of cladosporin-based inhibitors of malaria parasites0 aDesign synthesis and structural analysis of cladosporinbased inh cJUL a1777–17940 v73 a

Here we have described a systematic structure activity relationship (SAR) of a set of compounds inspired from cladosporin, a tool compound that targets parasite (Plasmodium falciparum) lysyl tRNA synthetase (KRS). Four sets of analogues, synthesized based on point changes in the chemical scaffold of cladosporin and other logical modifications and hybridizations, were assessed using high throughput enzymatic and parasitic assays along with in vitro pharmacokinetics. Co-crystallization of the most potent compound in our series (CL-2) with PfKRS revealed its structural basis of enzymatic binding and potency. Further, we report that CL-2 has performed better than cladosporin in terms of metabolic stability. It thus represents a new lead for further optimization toward the development of antimalarial drugs. Collectively, along with a lead compound, the series offers insights on how even the slightest chemical modification might play an important role in enhancing or decreasing the potency of a chemical scaffold.

1 aBabbar, Palak1 aDas, Pronay1 aManickam, Yogavel1 aMankad, Yash1 aYadav, Swati1 aParvez, Suhel1 aSharma, Amit1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/design-synthesis-and-structural-analysis-cladosporin-based-inhibitors-malaria-parasites02296nas a2200241 4500008004100000022001400041245011200055210006900167260000800236300001100244490000800255520148600263653001801749653002401767653001201791653001501803653001501818100002501833700001901858700002801877700001701905856013201922 2022 eng d a0166-685100aProfiling of metabolic alterations in mice infected with malaria parasites via high-resolution metabolomics0 aProfiling of metabolic alterations in mice infected with malaria cNOV a1115250 v2523 a

Background: Malaria infection can result in distinct clinical outcomes from asymptomatic to severe. The association between patho-physiological changes and molecular changes in the host, and their correlation with severity of malaria progression is not fully understood. Methods: In this study, we addressed mass spectrometry-based temporal profiling of serum metabolite levels from mice infected with Plasmodium berhgei (strain ANKA). Results: We show global perturbations and identify changes in specific metabolites in correlation with disease progression. While metabolome-wide changes were apparent in late-stage malaria, a subset of metabolites exhibited highly correlated changes with disease progression. These metabolites changed early on following infection and either continued or maintained the change as mice developed severe disease. Some of these have the potential to be sentinel metabolites for severe malaria. Moreover, glycolytic metabolites, purine nucleotide precursors, tryptophan and its bioactive derivatives were many fold decreased in late-stage disease. Interestingly, uric acid, a metabolic waste reported to be elevated in severe human malaria, increased with disease progression, and subsequently appears to be detoxified into allantoin. This detoxification mechanism is absent in humans as they lack the enzyme uricase. Conclusions: We have identified candidate marker metabolites that may be of relevance in the context of human malaria.

10aHost response10aInfectious diseases10amalaria10ametabolite10aPlasmodium1 aChhibber-Goel, Jyoti1 aShukla, Anurag1 aShanmugam, Dhanasekaran1 aSharma, Amit uhttps://library.ncl.res.in/content/profiling-metabolic-alterations-mice-infected-malaria-parasites-high-resolution-metabolomics03461nas a2200301 4500008004100000022001400041245012200055210006900177260000800246300001200254490000700266520249900273653002002772653001202792653002002804653001802824653001202842100002102854700001902875700001902894700001702913700002102930700002202951700001602973700001702989700002803006856012503034 2026 eng d a2328-895700aTargeted genomic surveillance unveils genetic variations linked to regional malaria drug resistance dynamics in India0 aTargeted genomic surveillance unveils genetic variations linked  cMAR aofag1060 v133 a

Background India has made substantial progress in reducing Plasmodium falciparum malaria cases and has set a target to eliminate malaria by 2030. Although artemisinin-based combination therapy (ACT) treatment remains effective, tracking regional differences in genetic variants associated with antimalarial resistance is required for effective drug policy implementation.Methods We analyzed 238 P. falciparum clinical samples from 6 Indian states by sequencing 15 parasite genes associated with reduced drug effectiveness. The method involved nanopore sequencing of target gene amplicons derived from dried blood spots using a highly-sensitive PfMDR15 surveillance panel.Results India's historical policy of artesunate-sulfadoxine-pyrimethamine in central India and artemether-lumefantrine in the Northeast has shaped contrasting resistance profiles. In the Northeast, chloroquine resistance persisted at high frequency (Pfcrt K76T and CVIET haplotype; Pfaat1 S258L), alongside quintuple and sextuple Pfdhfr-Pfdhps haplotypes conferring complete sulfadoxine-pyrimethamine resistance. Central India showed variable chloroquine resistance (parasites largely retained wild-type Pfcrt) and emerging lumefantrine tolerance (Pfmdr1 Y184F, Pfaat1 S258L). Interestingly, Delhi (Central India) parasites resembled profiles from the distant Northeast, which borders South East Asia. The detection of Pfaat1 S258L, previously reported only from Africa and associated with reduced lumefantrine susceptibility, suggests convergent evolution under ACT partner-drug pressure. No WHO-validated Pfk13 artemisinin resistance mutations were detected, supporting continued efficacy of ACT.Conclusions India's resistance landscape is fragmented, with signals of expanding lumefantrine tolerance and importation or evolution of globally relevant mutations. These findings highlight the importance of integrating molecular genomic surveillance into malaria control policy to monitor and protect ACT effectiveness and advance malaria elimination. Monitoring of drug resistance associated mutations in P. falciparum parasites is critical for effective drug treatment. We have demonstrated the use of a scalable genomic surveillance protocol for tracking drug resistance linked mutations in parasite genes from clinical isolates in India. The study suggests extensive regional diversity in antimalarial resistance profiles and provides the first hint of possible emergence of lumefantrine tolerance in India.

10adrug resistance10amalaria10aOxford nanopore10aP. falciparum10apfMDR151 aKhilari, Ajinkya1 aSharma, Shweta1 aBajpai, Manali1 aViswan, Anju1 aChaturvedi, Rini1 aMirdha, Bijay, R.1 aRahi, Manju1 aSharma, Amit1 aShanmugam, Dhanasekaran uhttps://library.ncl.res.in/content/targeted-genomic-surveillance-unveils-genetic-variations-linked-regional-malaria-drug