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Record W3021602689

Thiobarbituric acid a useful scaffold for medicinal chemistry.

2020· dissertation· en· W3021602689 on OpenAlexfundno aff
Sikabwe Noki

Bibliographic record

VenueResearchSpace (University of KwaZulu-Natal) · 2020
Typedissertation
Languageen
FieldChemistry
TopicChemical Synthesis and Reactions
Canadian institutionsnot available
FundersInstitute of Population and Public HealthMinisterio de Asuntos Económicos y Transformación Digital, Gobierno de EspañaInyuvesi Yakwazulu-NataliGeneralitat de CatalunyaKing Saud UniversityNational Research Foundation
KeywordsScaffoldThiobarbituric acidChemistryComputational biologyBiochemistryBiologyEngineeringBiomedical engineeringLipid peroxidationAntioxidant
DOInot available

Abstract

fetched live from OpenAlex

Due to the growth number of infectious diseases, a huge demand of new antimicrobial agents are required.In this regard, Thiobarbituric acid (TBA) moieties were explored.As its name indicates, TBA is the sulfur version of the barbituric acid.The work in barbituric moieties dated long ago in 1864 by Baeyer, when it was reported that these barbituric derivatives can be used as anesthetics, sedative or anticonvulsive agents.In the present work and taking advantage that TBA structure shows several points where diversity can be introduced, therefore several functionalities were introduced in the TBA analogues and their antimicrobial properties were studied in Gram-positive and Gram-negative bacteria.(Chapter 1) These are the chemical modifications explored: i) N-substitution, where this site can be substituted with a symmetrical substituents; ii) reaction at C-5 position owing to the high acidity of the protons which includes acylation, acetylation, Schiff bases, Knoevenagel condensation thioamide and enamine formation.The antimicrobial activity screening for the synthesized compounds were against Gram-positive (S. aureus and B. subtilus) and Gram negative (E. coli and P. aeruginosa) bacteria.Among all thiobabituric derivatives synthesized, Boc-Phe-TBA showed a promising activity, which confirms that TBA could be an excellent scaffold when combined with N-protected amino acids for developing antimicrobial compounds.(Chapter 2)The characterization of 20 thiobarbituric derivatives was carried out in different spectroscopy techniques such as: Nuclear Magnetic Resonance (NMR), Ultra violet spectroscopy, Infra-Red spectroscopy and single X-ray crystallography.In NMR characterization the acetylation of TBA was the most interesting due to the fact that this type of compound have the tendency of forming Enol and Keto tautomerism.This was proved by NMR and also by theoretical calculation, and the results confirm that the 1 H NMR for this compound (A01) showed resonance at 17.72 ppm (singlet) for OH.This indicate that the enol form is more stable than the keto form.In UV characterization due to the fact TBA derivatives are not known aromatic and yet they are UV active.Therefore the absorption of few TBA derivatives were study in different solvents hence these showed absorption iv at maximum wavelength (max) in the range of 322 -285 nm respectively.For IR characterization, these derivatives (A01, A02, A03, A04, A06, A10, A12, A13, A14 and A17) were evaluated, and showed absorption stretching frequency of thiocarbonyl (C=S) in three different ranges, 1395-1570 cm -1 , 1260-11420 cm -1 and 940 -1140 cm -1 .For X-ray crystallography, crystals of A01, A02, A06, A13, A17 and A18 were obtained by hot recrystallization from ethanol and the intramolecular H-Bonding formation was observed in all cases, intermolecular H-bonding was observed for A17.(Chapter 3) v DECLARATION I Plagiarism declaration I, Sikabwe Noki declare that 1.The research work reported in this thesis, except where otherwise indicated,

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.019

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0060.002

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.022
GPT teacher head0.252
Teacher spread0.230 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2020
Admission routes1
Has abstractno

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