The Affinity of Carboplatin to B-Vitamins and Nucleobases

Platinum compounds have found wide application in the treatment of various types of cancer and carboplatin is one of the main platinum-based drugs used as antitumor agents. The anticancer activity of carboplatin arises from interacting with DNA and inducing programmed cell death. However, such interactions may occur with other chemical compounds, such as vitamins containing aromatic rings with lone-pair orbitals, which reduces the anti-cancer effect of carboplatin. The most important aspect of the conducted research was related to the evaluation of carboplatin affinity to vitamins from the B group and the potential impact of such interactions on the reduction of therapeutic capabilities of carboplatin in anticancer therapy. Realized computations, including estimation of Gibbs Free Energies, allowed for the identification of the most reactive molecule, namely vitamin B6 (pyridoxal phosphate). In this case, the computational estimations indicating carboplatin reactivity were confirmed by spectrophotometric measurements.

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Does the Affinity of Cisplatin to B-Vitamins Impair the Therapeutic Effect in the Case of Patients with Lung Cancer-consuming Carrot or Beet Juice?

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190325150624 ◽

2019 ◽

Vol 19 (14) ◽

pp. 1775-1783 ◽

Cited By ~ 2

Author(s):

Beata Szefler ◽

Przemysław Czeleń ◽

Adam Szczepanik ◽

Piotr Cysewski

Keyword(s):

Computational Study ◽

Lone Pair ◽

B Vitamins ◽

Basis Set ◽

Free Energies ◽

Aromatic Rings ◽

Reaction Field ◽

Vitamin B Group ◽

Solvation Free Energies ◽

Derivatives Of

Background: Cisplatin (CisPt) has a well-recognized anticancer activity by interacting with DNA and inducing programmed cell death. However, theoretical studies performed on the molecular level suggest that such nonspecific interactions can also take place with many competitive compounds, such as vitamins containing aromatic rings with lone-pair orbitals. Objective: This work is a theoretical study on the initial Pt-N7(N1) bond formation with vitamins from B group and their comparison with values characterizing native purines. Methods: Geometries of studied structures were optimized with an aid of Gaussian 09 using the B3LYP functional with the 6-31G** basis set. Atomic orbitals of platinum were represented by the lanl2dz basis. Solvation free energies were evaluated by a self-consistent reaction field (SCRF) approach. A dielectric constant of 78 for water was used in the PCM continuum model computations along with radii Bondii. Results: The affinities of mono-aqua cis~[Pt(NH3)2Cl(H2O)]+ and di-aqua cis~ [Pt(NH3)2(H2O)2]2+ derivatives of Cisplatinum toward compounds belonging to the group of eight B vitamins were studied and compared to interactions with canonical purines. All the values of ΔGr unambiguously indicate that reactions with cisPt-diaqua are more preferable, but the comparison of ΔGr values obtained for compounds from vitamin B group and the ones characterizing complexes created by Guanine molecules indicates higher affinity of cisPt monomers toward purines. Conclusion: Based on the observations, the regular intake of vitamin-rich beetroot or carrot juices is strongly discouraged during anticancer therapy using CisPt drug. To confirm the results of the performed computational study, detailed clinical trials should be performed.

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Does the Oxazolidinone Derivatives Constitute a Functional Approach for Cancer Therapy?

Clinical Cancer Drugs ◽

10.2174/2212697x07999200807210936 ◽

2020 ◽

Vol 7 (2) ◽

pp. 95-106

Author(s):

Eduardo Augusto Vasconcelos de Freitas Ramalho ◽

Marina Galdino da Rocha Pitta ◽

Hernando de Barros Siqueira Neto ◽

Ivan da Rocha Pitta

Keyword(s):

Cell Lines ◽

Antitumor Agents ◽

Partial Agonist ◽

Drug Repurposing ◽

Antitumor Agent ◽

Short Review ◽

Sphingolipid Metabolism ◽

Solid Cancer ◽

Ppar Γ ◽

Anti Cancer

In the last four decades, the emphasis was laid on the research of small organic molecules with potential anti-cancer activity. Linezolid was the first oxazolidinone derivative approved by FDA for MRSA treatment. Despite its major role in antimicrobial activity, these molecules display other properties, also serving as an antitumor agent. The importance of drug repurposing could be highlighted by the use of Oxazolidinone derivatives in pre-clinical studies, which are able to act through different pathways, such as partial agonist of transcription factor PPAR-γ, an inhibitor of key enzymes related to hormone-dependent disorders and even on sphingolipid metabolism as well. The purpose of this short review is to discuss the application of oxazolidinone derivatives as an antitumor agent by highlighting the most promising molecules studied by many research groups worldwide. Main biological activity against several tumor cell lines, including hematopoietic and solid cancer cell lines have been discussed. In addition, this study intends to report how different types of oxazolidinone derivatives can act as antitumor agents describing their distinct mechanisms of action based on their targets.

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COMMITTEE ON NUTRITION

PEDIATRICS ◽

10.1542/peds.38.6.1068 ◽

1966 ◽

Vol 38 (6) ◽

pp. 1068-1076

Author(s):

Keyword(s):

Vitamin B6 ◽

Pyridoxal Phosphate ◽

Normal Population ◽

Clinical Signs ◽

Normal Activity ◽

Limited Information ◽

Adequate Intake ◽

Time Data ◽

Binding Properties ◽

Adequate Diet

Because of the limited information available it is not possible to derive precise figures for daily requirements of vitamin B6 in infants and children at this time. Data currently available suggest that the daily need in childhood is 0.5 to 1.5 mg and in adolescence is 1.5 to 2 mg. The requirement in infancy is clearly related to protein intake and is 20µg/gm of dietary protein. Requirements of a few individuals will undoubtedly be higher than the estimates for the normal population. Some of these patients will manifest frank biochemical and clinical signs of deficiency which will usually be promptly reversed by administration of small additional amounts of pyridoxine. Another group of patients will require large amounts of the vitamin to balance the heritable alteration in binding properties of a specific apoenzyme requiring pyridoxal phosphate for normal activity. It would appear that most infants, children and adults will have little difficulty in achieving an adequate intake of vitamin B6 if they receive what is considered to be in other respects an adequate diet.

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APPLICATION OF EXTRACTION METHOD FOR ISOLATION OF BIOGENIC SURFACE-ACTIVE RHAMNOLIPIDS

Proceedings of the Shevchenko Scientific Society. Series Сhemical Sciences ◽

10.37827/ntsh.chem.2020.60.007 ◽

2020 ◽

Vol 2020 (60) ◽

pp. 7-13

Author(s):

Іlоna KARPENKO ◽

◽

Galyna MIDYANA ◽

Olena KARPENKO ◽

Igor SEMENIUK ◽

...

Keyword(s):

Lone Pair ◽

Physicochemical Characteristics ◽

Extraction Process ◽

Pseudomonas Sp ◽

Free Energies ◽

Isolation And Purification ◽

Priority Task ◽

Surface Active ◽

Modern Biotechnology ◽

The Relationship

The priority task of modern biotechnology is development of the rational technologies for the microbial synthesis of practically important products. Among these products, a significant place belongs to surfactants (biosurfactants), which are widely used in many sectors of the economy. The most problematic stage of the biosurfactants production is isolation from the post fermentative cultural liquid of bacteria-producers. Improving the efficiency of the biosurfactants production is highly dependent on rational approaches to the target products isolation. In this regard, there is an increasing need for rational, scientifically substantiated methods for their isolation and purification. Therefore, the aim of the presented work was to determine the optimal extractants for the isolation of rhamnolipid surfactants – metabolites of bacteria of Pseudomonas sp. PS-17 strain. For this purpose, the extraction process of rhamnolipids from the post fermentative cultural liquid supernatant has been investigated. The optimal extractants were selected among 13 organic solvents of different nature. Processing of the obtained experimental data by the method of multi-parameter equations of linearity of free energies (modified Koppel-Palm equation) made it possible to establish the relationship between the physicochemical properties of the extractants and amounts of the biosurfactants which were isolated from cultural liquid supernatant. It was shown that the data on the rhamnolipids extraction are adequately associated with the physicochemical characteristics of the solvents using a six-parameter linear equation. It was determined that the polarizability and molar volume are the main properties of solvents that affect the extraction process. The best extractants for the rhamnolipids isolation from cultural liquid supernatant of the Pseudomonas sp. PS-17 strain are the ethers. It can be explained by the presence of a lone pair of the electrons of oxygen in its molecule. The obtained results of the study are of scientific interest for isolation of the important and perspective biotechnological products – surface-active substances.

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The Alkaline Phosphatase (ALPL) Locus Is Associated with B6 Vitamer Levels in CSF and Plasma

Genes ◽

10.3390/genes10010008 ◽

2018 ◽

Vol 10 (1) ◽

pp. 8 ◽

Cited By ~ 3

Author(s):

Loes Loohuis ◽

Monique Albersen ◽

Simone de Jong ◽

Timothy Wu ◽

Jurjen Luykx ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Vitamin B6 ◽

Pyridoxal Phosphate ◽

Genome Wide Association Study ◽

Active Form ◽

Minor Allele ◽

Chromosome 1 ◽

Joint Analysis ◽

Genome Wide ◽

A Genome

The active form of vitamin B6, pyridoxal phosphate (PLP), is essential for human metabolism. The brain is dependent on vitamin B6 for its neurotransmitter balance. To obtain insight into the genetic determinants of vitamin B6 homeostasis, we conducted a genome-wide association study (GWAS) of the B6 vitamers pyridoxal (PL), PLP and the degradation product of vitamin B6, pyridoxic acid (PA). We collected a unique sample set of cerebrospinal fluid (CSF) and plasma from the same healthy human subjects of Dutch ancestry (n = 493) and included concentrations and ratios in and between these body fluids in our analysis. Based on a multivariate joint analysis of all B6 vitamers and their ratios, we identified a genome-wide significant association at a locus on chromosome 1 containing the ALPL (alkaline phosphatase) gene (minimal p = 7.89 × 10−10, rs1106357, minor allele frequency (MAF) = 0.46), previously associated with vitamin B6 levels in blood. Subjects homozygous for the minor allele showed a 1.4-times-higher ratio between PLP and PL in plasma, and even a 1.6-times-higher ratio between PLP and PL in CSF than subjects homozygous for the major allele. In addition, we observed a suggestive association with the CSF:plasma ratio of PLP on chromosome 15 (minimal p = 7.93 × 10−7, and MAF = 0.06 for rs28789220). Even though this finding is not reaching genome-wide significance, it highlights the potential of our experimental setup for studying transport and metabolism across the blood–CSF barrier. This GWAS of B6 vitamers identifies alkaline phosphatase as a key regulator in human vitamin B6 metabolism in CSF as well as plasma. Furthermore, our results demonstrate the potential of genetic studies of metabolites in plasma and CSF to elucidate biological aspects underlying metabolite generation, transport and degradation.

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Antitumor Activity of Pt(II), Ru(III) and Cu(II) Complexes

Molecules ◽

10.3390/molecules25153492 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3492

Author(s):

Katarzyna Gałczyńska ◽

Zuzanna Drulis-Kawa ◽

Michał Arabski

Keyword(s):

Cell Cycle ◽

Transition Metal ◽

Metal Complexes ◽

Transition Metal Complexes ◽

Antitumor Agents ◽

Current Knowledge ◽

Biological Activities ◽

Chemical Compounds ◽

Cell Cycle Inhibition ◽

Therapeutic Compounds

Metal complexes are currently potential therapeutic compounds. The acquisition of resistance by cancer cells or the effective elimination of cancer-affected cells necessitates a constant search for chemical compounds with specific biological activities. One alternative option is the transition metal complexes having potential as antitumor agents. Here, we present the current knowledge about the application of transition metal complexes bearing nickel(II), cobalt(II), copper(II), ruthenium(III), and ruthenium(IV). The cytotoxic properties of the above complexes causing apoptosis, autophagy, DNA damage, and cell cycle inhibition are described in this review.

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The relationship between plasma albumin, alkaline phosphatase and pyridoxal phosphate concentrations in plasma and red cells: Implications for assessing vitamin B6 status

Clinical Nutrition ◽

10.1016/j.clnu.2019.12.012 ◽

2020 ◽

Vol 39 (9) ◽

pp. 2824-2831 ◽

Cited By ~ 1

Author(s):

Dinesh Talwar ◽

Anthony Catchpole ◽

John M. Wadsworth ◽

Barry J. Toole ◽

Donald C. McMillan

Keyword(s):

Alkaline Phosphatase ◽

Vitamin B6 ◽

Pyridoxal Phosphate ◽

Red Cells ◽

Plasma Albumin ◽

The Relationship

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The energy landscape concept and its implications for synthesis planning

Pure and Applied Chemistry ◽

10.1515/pac-2014-0212 ◽

2014 ◽

Vol 86 (6) ◽

pp. 883-898 ◽

Cited By ~ 6

Author(s):

Martin Jansen

Keyword(s):

Energy Landscape ◽

Chemical Compounds ◽

Materials Chemistry ◽

Energy Landscapes ◽

Free Energies ◽

Lack Of Control ◽

Synthesis Planning ◽

Materials Research ◽

Potential Energy Landscapes ◽

Almost All

AbstractSynthesis of novel solids, in a chemical sense, is one of the spearheads of innovation in materials research. However, such an undertaking is substantially impaired by lack of control and predictability. We present a concept that points the way towards rational planning of syntheses in solid state and materials chemistry. The foundation of our approach is the representation of the whole material world, i.e., the known and not-yet-known chemical compounds, on an energy landscape, which implies information about the free energies of these configurations. From this it follows at once that all chemical compounds capable of existence (both thermodynamically stable and metastable ones) are already present in virtuo in this landscape. For the first step of synthesis planning, i.e., the identification of candidates that are capable of existence, we computationally search the respective potential energy landscapes for (meta)stable structure candidates. Recently we have extended our techniques to finite temperatures and pressures and calculated phase diagrams, including metastable manifestations of matter, without resorting to any experimental pre-information. The conception developed is physically consistent, and its feasibility has been proven. Applying appropriate experimental tools has enabled us to realize, e.g., elusive Na3 N, including almost all of its predicted polymorphs, many years after the predictions were published.

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