Publications by authors named "Sucheta Kudrimoti"

9 Publications

  • Page 1 of 1

Synthesis and characterization of barbarin, a possible source of unexplained aminorex identifications in forensic science.

Drug Test Anal 2020 Oct 26;12(10):1477-1482. Epub 2020 Aug 26.

Department of Toxicology and Cancer Biology and the Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.

Aminorex is a US DEA Schedule 1 controlled substance occasionally detected in racing horses. A number of aminorex identifications in sport horses were thought to have been caused by exposure to plant sources of aminorex. Glucobarbarin, found in plants of the Brassicaceae family, has been suggested as a potential proximate chemical source by being metabolized in the plant or the horse to aminorex. In Brassicaceae, glucobarbarin is hydrolyzed by myrosinase to yield barbarin, which serves as an insect repellant and/or attractant and is structurally related to aminorex. The synthesis, purification, and characterization of barbarin is now reported for use as a reference standard in aminorex related research concerning equine urinary identifications of aminorex and also for possible use in equine administration experiments. Synthesis of barbarin was performed via ring closure between phenylethanolamine and carbon disulfide in tetrahydrofuran with the catalyst pyridine under reflux. The reaction yielded a white crystalline substance that was purified and chemically characterized as barbarin for use as a Certified Reference Standard or for studies related to equine aminorex identification.
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http://dx.doi.org/10.1002/dta.2883DOI Listing
October 2020

Aminorex identified in horse urine following consumption of a preliminary report.

Ir Vet J 2019 23;72:15. Epub 2019 Dec 23.

3The Maxwell H. Gluck Equine Research Center and Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40546 USA.

Background: Aminorex, (RS)-5- Phenyl-4,5-dihydro-1,3-oxazol-2-amine, is an amphetamine-like anorectic and in the United States a Drug Enforcement Administration [DEA] Schedule 1 controlled substance. Aminorex in horse urine is usually present as a metabolite of Levamisole, an equine anthelmintic and immune stimulant. Recently, Aminorex identifications have been reported in horse urine with no history or evidence of Levamisole administration. Analysis of the urine samples suggested a botanical source, directing attention to the Brassicaceae plant family, with their contained GlucoBarbarin and Barbarin as possible sources of Aminorex. Since horsepersons face up to a 1 year suspension and a $10,000.00 fine for an Aminorex identification, the existence of natural sources of Aminorex precursors in equine feedstuffs is of importance to both individual horsepersons and the industry worldwide.

Results: Testing the hypothesis that Brassicaceae plants could give rise to Aminorex identifications in equine urine we botanically identified and harvested flowering Kentucky , ("Yellow Rocket") in May 2018 in Kentucky and administered the plant orally to two horses. Analysis of post-administration urine samples yielded Aminorex, showing that consumption of Kentucky can give rise to Aminorex identifications in equine urine.

Conclusions: Aminorex has been identified in post administration urine samples from horses fed freshly harvested flowering Kentucky , colloquially "Yellow Rocket". These identifications are consistent with occasional low concentration identifications of Aminorex in equine samples submitted for drug testing. The source of these Aminorex identifications is believed to be the chemically related Barbarin, found as its precursor GlucoBarbarin in Kentucky and related Brassicaceae plants worldwide.
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http://dx.doi.org/10.1186/s13620-019-0153-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929286PMC
December 2019

A cluster of trace-concentration methamphetamine identifications in racehorses associated with a methamphetamine-contaminated horse trailer: A report and analysis.

Can Vet J 2016 Aug;57(8):860-4

1711 Lakefield North Court, Wellington, Florida 33414, USA (Brewer); American Association of Medical Review Officers, 17 Running Brook Ct., Durham, North Carolina 27713, USA (Shults); Frontier BioPharm, PO Box 614, Richmond, Kentucky 40476, USA (Eisenberg); Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 40546, USA (Kudrimoti, Machin, Tobin); Equine Integrated Medicine, PLC 4904 Ironworks Road, Georgetown, Kentucky 40324, USA (Fenger); Industrial Laboratories, 4046 Youngfield Street, Wheat Ridge, Colorado 80033, USA (Hartman, Wang); CanAlt Health Labs, 242 Applewood, Unit 3, Vaughan, Ontario (Beaumier).

Three low concentration methamphetamine "positive" tests were linked to use of a methamphetamine-contaminated trailer to transport the affected horses. This incident establishes methamphetamine as a human-use substance that can inadvertently enter the environment of racing horses, resulting in urinary methamphetamine "positives;" an interim regulatory cut-off of 15 ng/mL for methamphetamine in post-race urine is proposed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944564PMC
August 2016

Structure-Based Discovery of a Novel Pentamidine-Related Inhibitor of the Calcium-Binding Protein S100B.

ACS Med Chem Lett 2012 Dec 25;3(12):975-979. Epub 2012 Sep 25.

Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201.

Molecular Dynamics simulations of the pentamidine-S100B complex, where two molecules of pentamidine bind per monomer of S100B, were performed in an effort to determine what properties would be desirable in a pentamidine-derived compound as an inhibitor for S100B. These simulations predicted that increasing the linker length of the compound would allow a single molecule to span both pentamidine binding sites on the protein. The resulting compound, SBi4211 (also known as heptamidine), was synthesized and experiments to study its inhibition of S100B were performed. The 1.65 Å X-ray crystal structure was determined for Ca(2+)-S100B-heptamdine and gives high-resolution information about key contacts that facilitate the interaction between heptamidine and S100B. Additionally, NMR HSQC experiments with both compounds show that heptamidine interacts with the same region of S100B as pentamidine. Heptamidine is able to selectively kill melanoma cells with S100B over those without S100B, indicating that its binding to S100B has an inhibitory effect and that this compound may be useful in designing higher-affinity S100B inhibitors as a treatment for melanoma and other S100B-related cancers.
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http://dx.doi.org/10.1021/ml300166sDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524579PMC
December 2012

Structure-activity relationship and mechanism of action studies of manzamine analogues for the control of neuroinflammation and cerebral infections.

J Med Chem 2010 Jan;53(1):61-76

Department of Pharmacognosy, The University of Mississippi, Oxford, Mississippi 38677, USA.

Structure-activity relationship studies were carried out by chemical modification of manzamine A (1), 8-hydroxymanzamine A (2), manzamine F (14), and ircinal isolated from the sponge Acanthostrongylophora. The derived analogues were evaluated for antimalarial, antimicrobial, and antineuroinflammatory activities. Several modified products exhibited potent and improved in vitro antineuroinflammatory, antimicrobial, and antimalarial activity. 1 showed improved activity against malaria compared to chloroquine in both multi- and single-dose in vivo experiments. The significant antimalarial potential was revealed by a 100% cure rate of malaria in mice with one administration of 100 mg/kg of 1. The potent antineuroinflammatory activity of the manzamines will provide great benefit for the prevention and treatment of cerebral infections (e.g., Cryptococcus and Plasmodium). In addition, 1 was shown to permeate across the blood-brain barrier (BBB) in an in vitro model using a MDR-MDCK monolayer. Docking studies support that 2 binds to the ATP-noncompetitive pocket of glycogen synthesis kinase-3beta (GSK-3beta), which is a putative target of manzamines. On the basis of the results presented here, it will be possible to initiate rational drug design efforts around this natural product scaffold for the treatment of several different diseases.
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http://dx.doi.org/10.1021/jm900672tDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834284PMC
January 2010

Structure-activity relationship studies of manzamine A: amidation of positions 6 and 8 of the beta-carboline moiety.

Bioorg Med Chem 2009 Nov 19;17(22):7775-82. Epub 2009 Sep 19.

Department of Pharmacognosy, The School of Pharmacy, The University of Mississippi, Oxford, MS 38677, USA.

Twenty manzamine amides were synthesized and evaluated for in vitro antimalarial and antimicrobial activities. The amides of manzamine A (1) showed significantly reduced cytotoxicity against Vero cells, although were less active than 1. The structure-activity analysis showed that linear, short alkyl groups adjacent to the amide carbonyl at position 8 are favored for antimalarial activity, while bulky and cyclic groups at position 6 provided the most active amides. Most of the amides showed potent activity against Mycobacterium intracellulare. The antimicrobial activity profile for position 8 series was similar to that for antimalarial activity profile, in which linear, slightly short alkyl groups adjacent to the amide carbonyl showed improved activity. Two amides 14 and 21, which showed potent antimalarial activity in vitro against Plasmodium falciparum were further evaluated in vivo in Plasmodium berghei infected mice. Oral administration of 14 and 21 at the dose of 30mg/kg (once daily for three days) caused parasitemia suppression of 24% and 62%, respectively, with no apparent toxicity.
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http://dx.doi.org/10.1016/j.bmc.2009.09.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4883699PMC
November 2009

Semisynthetic latrunculin B analogs: studies of actin docking support a proposed mechanism for latrunculin bioactivity.

Bioorg Med Chem 2009 Nov 16;17(21):7517-22. Epub 2009 Sep 16.

Department of Pharmacognosy, The University of Mississippi, University, MS 38677-1848, United States.

Latrunculins are unique macrolides containing a thiazolidinone moiety. Latrunculins A, B and T and 16-epi-latrunculin B were isolated from the Red Sea sponge Negombata magnifica. N-Alkylated, O-methylated analogs of latrunculin B were synthesized and biological evaluation was performed for antifungal and antiprotozoal activity. The natural latrunculins showed significant bioactivity, while the semisynthetic analogs did not. Docking studies of these analogs into the X-ray crystal structure of G-actin showed that, in comparison with latrunculins A and B, N-alkylated latrunculins did not dock satisfactorily. This suggests that the analogs do not fit well into the active site of G-actin due to steric clashes and provides an explanation for the absence of bioactivity.
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http://dx.doi.org/10.1016/j.bmc.2009.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782694PMC
November 2009

Novel acyl phosphate mimics that target PlsY, an essential acyltransferase in gram-positive bacteria.

ChemMedChem 2008 Dec;3(12):1936-45

Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 847 Monroe Ave, Memphis, TN 38163, USA.

PlsY is a recently discovered acyltransferase that executes an essential step in membrane phospholipid biosynthesis in Gram- positive bacteria. By using a bioisosteric replacement approach to generate substrate-based inhibitors of PlsY as potential novel antibacterial agents, a series of stabilized acyl phosphate mimetics, including acyl phosphonates, acyl alpha,alpha-difluoromethyl phosphonates, acyl phosphoramides, reverse amide phosphonates, acyl sulfamates, and acyl sulfamides were designed and synthesized. Several acyl phosphonates, phosphoramides, and sulfamates were identified as inhibitors of PlsY from Streptococcus pneumoniae and Bacillus anthracis. As anticipated, these inhibitors were competitive inhibitors with respect to the acyl phosphate substrate. Antimicrobial testing showed the inhibitors to have generally weak activity against Gram-positive bacteria with the exception of some acyl phosphonates, reverse amide phosphonates, and acyl sulfamates, which had potent activity against multiple strains of B. anthracis.
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http://dx.doi.org/10.1002/cmdc.200800218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722063PMC
December 2008
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