Chromatographic Separations and Analysis: Supercritical Fluid Chromatography for Chiral Analysis and Semi-Preparative Purification

Berger, Terry A.; Berger, Blair K.; Kogelman, Kimber

doi:10.1016/b978-0-32-390644-9.00013-5

Cited by 4 publications

(4 citation statements)

References 59 publications

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“…Because of this, further categorization would need to occur as more hormone receptor inhibitor medications are approved by the FDA. It is also notable that in kinase inhibitors, a logP value between 3 and 5 is likely to indicate that a drug in early development suffices in the category of lipophilicity [6]. A trend of having 3 or 4 hydrogen bond donors in the FDA-approved proteasome inhibitor anticancer medications was seen, likely indicating that with a compatible structure, a proteasome inhibitor drug in early development should have a similar number of hydrogen bond donors.…”

Section: Discussionmentioning

confidence: 99%

“…These drugs can be separated into classes based on which proteins they inhibit; this review covers kinase inhibitors, hormone receptor inhibitors, proteasome inhibitors, PARP (poly ADP-ribose polymerase) inhibitors, and HDAC (histone deacetylase) inhibitors [4]. The action of inhibition prevents or diminishes the oncogenic activity of a specific enzymefor example, PARP inhibitors prevent the PARP enzyme from repairing damaged cells, resulting in cell death, an intended outcome for cancer cells in cancer treatment [4,5] between the main families of chemotherapy inhibitor medications using PubChem as my database for metric compiling [6,7]. These metrics were collected for kinase inhibitors (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Chemical and Physical Metrics in Establishing Benchmarks for Chemotherapy Drug Efficacy

Karkafi

2024

Preprint

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Small-molecule enzyme inhibitors have been employed as chemotherapy medications for decades, proving to be valuable tools in inhibiting oncogenic mechanisms at the molecular level [1]. The prevalence of these inhibitors as drugs allows for extensive cross-comparison of their properties, both chemical and dynamic. Many of these properties are intertwined with binding energy dynamics and the mobility of a drug throughout cell membranes, defining their efficiency and capability in being transported to a target enzyme and binding to said enzyme to inhibit its activity [2]. In this paper, I compare chemical and physical properties of FDA-approved cancer chemotherapy medications in five families of enzyme inhibitors to identify metric-based trends or benchmarks that may estimate the viability or extent of efficacy for a given chemotherapy medication in early research and development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chemical and Physical Metrics in Establishing Benchmarks for Chemotherapy Drug Efficacy

Karkafi

2024

Preprint

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“…In order to assess if a new molecule is a good candidate for the oral route, logP should be between 0 and 5. LogP is the log of the partition coefficient of a solute between octanol and water at near-infinite dilution and is, therefore, also defined as the ratio of the concentration of the unionized compound at equilibrium between organic and aqueous phases [ 57 , 58 ]. The higher the lipophilicity, the less soluble is the compound in water.…”

Section: Methodsmentioning

confidence: 99%

The First Physiologically Based Pharmacokinetic (PBPK) Model for an Oral Vaccine Using Alpha-Tocopherol as an Adjuvant

Saldanha,

Vale

2023

Pharmaceutics

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Oral vaccines represent many advantages compared to standard vaccines. They hold a simple method of administration and manufacturing process. In addition to these, the way they can induce immune responses makes these a promising technology for the pharmaceutical industry and represents a new hope to society. Physiologically based pharmacokinetics (PBPK) has been used in support of drug development to predict the pharmacokinetics of the compound, considering the patient’s physiology. Despite PBPK studies now being widely used, there are very few models in the literature that support vaccine development. Therefore, the goal of this article was to determine how PBPK could support vaccine development. The first PBPK model for an oral vaccine using alpha-tocopherol as a vaccine adjuvant was built. LogP is the parameter that influences the delivery of alpha-tocopherol into the tissues more. Having a high LogP means it accumulates in adipose tissue and is slowly metabolized. The ideal formulation to include alpha-tocopherol in an oral vaccine would incorporate nanoparticles in a capsule, and the dosage of the compound would be 150 mg in a volume of 200 mL. This article aims to determine if alpha-tocopherol, as a well-known adjuvant for intramuscular injection vaccines, could be used as an adjuvant to oral vaccines. This model was built considering the conditions and requirements needed for designing an oral vaccine. This implies making sure the antigen and adjuvants reach the main target by overcoming the challenges of the gastrointestinal tract. The main parameters that would need to be included in a formulation using alpha-tocopherol as an adjuvant were determined.

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“…For instance, the hydrophobicity-related Log P (Partition coefficient), CMR (Calculated molar refractivity), MR (Remanent magnetization) and tPSA (topological Polar Surface Area) of PGG and PVG were observed using Chemdraw. The logP is a negative value for hydrophilic compounds (higher affinity for the aqueous phase), and a positive value for hydrophilic compounds [40]; CMR is a calculated molar refractivity of one mole of a substance [41]; MR is the magnetization that remains after removal a sufficiently large field to reach the saturation magnetization [42] and tPSA is the surface sum over all polar atoms or molecules, primarily oxygen and nitrogen, also including their attached hydrogen atoms [43]. In addition to these things, the values of Henry's law, heat of form, dipole moment, CLogP, and other important parameters were also renowned.…”

Section: Simulation Methodsmentioning

confidence: 99%

A quantum chemistry background of sickle cell anemia and gaps in antisickling drug development

Suhail,

Usmani,

Ahmad

2023

Eur J Chem

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Sickle cell anemia disease has been a great challenge for the world in the present situation. It occurs only due to the polymerization of sickle hemoglobin (HbS) having Pro-Val-Glu (PVG) typed mutation, while the polymerization does not occur in normal hemoglobin (HbA) having Pro-Glu-Glu (PGG) residues. According to data from the literature, Val-beta6 of Pro-Val-Glu is hydrophobic in nature, which appears to fit into a hydrophobic pocket in the adjacent HbS. After the insertion of Pro-Val-Glu into a hydrophobic pocket on the adjacent HbS, the polymerization is started. This is a questionable point on how the replacement of glutamic acid with valine in HbS makes it more reactive to fit into a hydrophobic pocket on adjacent HbS for polymerization. No data from the literature on the reactivity of HbS for polymerization was found yet. This is the first time that the theoretical calculation was done in both HbA and HbS where they were structurally different. After that, a comparative study between PVG and PGG was done at quantum level for the evaluation of the reactivity to fit into a hydrophobic pocket on adjacent HbS. At a quantum level, it was found that the HOMO-LUMO gap of Pro-Val-Glu was lower than that of Pro-Glu-Glu. According to the data from the literature, the lesser HOMO-LUMO gap promotes the initiation of the polymerization reaction. On the basis of the results, it was also shown how the mutation point (Pro-Val-Glu) in HbS becomes more reactive to polymerization, whereas Pro-Glu-Glu in HbA does not. The computational method developed for the first time will be very helpful not only for molecular biologists but also for computational and medicinal chemists. Additionally, the required modifications based on gaps in anti-sickling drug development are also suggested in the presented article.

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Chromatographic Separations and Analysis: Supercritical Fluid Chromatography for Chiral Analysis and Semi-Preparative Purification

Cited by 4 publications

References 59 publications

Chemical and Physical Metrics in Establishing Benchmarks for Chemotherapy Drug Efficacy

Chemical and Physical Metrics in Establishing Benchmarks for Chemotherapy Drug Efficacy

The First Physiologically Based Pharmacokinetic (PBPK) Model for an Oral Vaccine Using Alpha-Tocopherol as an Adjuvant

A quantum chemistry background of sickle cell anemia and gaps in antisickling drug development

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