Dr. Pradip K. Bhowmik
Professor, Department of Chemistry and Biochemistry, University of Nevada Las Vegas,  Nevada, USA.

ISBN 978-93-90768-93-6 (Print)
ISBN 978-93-90768-91-2 (eBook)
DOI: 10.9734/bpi/cacb/v3

This book covers key areas of chemistry and biochemistry research. The contributions by the authors include neuroendocrine tumor, degradation derivative, impurity identification, tandem mass spectrometry, microwave irradiation, eco-friendly reactions, biological activity, mono and bimetallic nanoparticles, capping effect, HPTC fingerprinting, antioxidant bioefficacy, Signal transduction, molecular vibration, resonance recognition, infrared radiation, molecular interaction, toxicity, anti-diabetes, desulfurization, homogeneous catalysis, Zipf’s Law, Proteoforms Numbers, Biomarkers, High-grade Glioblastoma, two-dimensional electrophoresis, mass spectrometry, environmental epigenetics, epigenetic marks, signal integration, molecular mechanisms, Schiff bases, metal complexes, antimicrobial activity, antitumor activity, nonlinear optical properties. This book contains various materials suitable for students, researchers and academicians in the field of chemistry and biochemistry.


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Recent Approach on Determination of Impurities and Degradation Products/Causes for m-Iodobenzylguanidine Using HPLC-Tandem Mass Spectrometry

Wei-Hsi Chen, Yu Chang, Ching-Yun Lee, Shiu-Wen Liu, Wen-Ching Wu, Tsai-Yueh Luo

Current Advances in Chemistry and Biochemistry Vol. 3, 4 March 2021, Page 1-16

m-Iodobenzylguanidine hemisulfate (MIBGHS) is a precursor in the preparation of radioiodine-labeled m-iodobenzylguanidine (MIBG), which is used as a radio-imaging and therapy agent for neuroendocrine tumors and myocardial sympathetic nerve function. To ensure the quality and efficacy of the medicine and prevent side effects, the precursor purity, source of impurity, and derivatives have to be determined. In this study, the purity of synthesized MIBGHS and the amount of contaminants therein were determined by high-performance liquid chromatography and ultraviolet detection, gradient eluted by ammonium formate aqueous solution and acetonitrile mobile phase on both C8 and phenyl type column. The impurities were identified on the basis of molecular and fragmented ion mass spectra using of electrospray ionization triple quadrupole tandem mass spectrometry. The results revealed the presence of process- related impurities including m-bromobenzylguanidine (MBrBG) and overreacted byproducts. Stress test results indicated that MIBGHS is stable under acidic and dry thermal conditions for at least 72 h but MIBG aqueous solution was decomposes slowly when exposed to UV light, thermal, oxidative and alkaline environments. Thus, m-iodobenzylamine, the starting material intended for the synthesis of MIBGHS should be analyzed to ensure that it is free from m-bromobenzylamine impurity. Stored under normal condition (-18°C), MIBGHS is stable for at least 12 months. The chemically labile guanidine and amine groups in MIBGHS are the major causes of its instability, while iodide loss from the phenyl group is a minor cause. All contaminants, derivatives, and degenerates derived from the reaction activity of the guanidine or amine groups, and the weak phenyl-iodine bond of MIBG, they are non-toxic under normal medicinal dose, but may reduce the effective dose of radioiodine-labeled MIBG.

Microwave Assisted Reactions for Synthesis of Bioactive Azaheterocycles

Ramona Danac, Dorina Amariucai-Mantu, Vasilichia Antoci, Gheorghita Zbancioc, Violeta Mangalagiu, Ionel I. Mangalagiu

Current Advances in Chemistry and Biochemistry Vol. 3, 4 March 2021, Page 17-50

Over the past years, azaheterocycles have received an immense attention because of their notable occurrence in many natural and synthetic drugs, and their large variety of biological activities. In the same time, there is a big need of greener and eco-friendly synthetic approaches in order to respond the actual demands of the changing environment. In this context, the development of more efficient synthetic protocols for azaheterocycles is a big challenge and microwave irradiation represents one of the most effective nonconventional alternatives to the classical methods used in medicinal chemistry. This book chapter presents an overview of the recent advances of microwave assisted reactions and its advantages in synthesis of bioactive 5- and 6-membered ring azaheterocycles (containing one to four nitrogen atoms). Representative considerations regarding mechanistic aspects, differences between conventional and microwave –assisted syntheses and biological activity of the obtained products are discussed.

An In-vitro and In-vivo Study of Antioxidant Potential of Green Synthesized Flavonoid Loaded Mono and Bimetallic Nanoparticles

Mukti Sharma, Saurabh Yadav, Narayanan Ganesh, Man Mohan Srivastava, Shalini Srivastava

Current Advances in Chemistry and Biochemistry Vol. 3, 4 March 2021, Page 51-67

Remarkable success of nanotechnology has un-wrapped the visualization for developing mono and multimetallic nanoparticles exhibiting a wide range of applications because of their unique behavior. Gold and silver nanoparticles have received significant progress particularly in the area of biomedical research. The study demonstrates a single step environmentally benign approach to fabricate mono (Au, Ag) and bimetallic (Au-Ag) nanoparticles using flavonoids, extracted from the bark of the plant Madhuca longifolia. The effect of the architecture has been studied on the behavior of mono (Au, Ag) and bimetallic (Au-Ag) nanoparticles towards antioxidant bio-efficacy. Bimetallic (Au-Ag) nanoparticles have persuaded comparatively higher antioxidant bio-efficacy than monometallic nanoparticles. Based on our experiments and relevant information, a tentative mechanism has been suggested for the higher antioxidant bio-efficacy of bimetallic nanoparticles. The capping of medicinally important flavonoids on the freshly generated metal nanoparticles for the enhancement in the target bio-efficacy has been proved using HPTLC fingerprinting. The proposed green nanotechnological strategy for the fabrication of bimetallic nanoparticles seems to be an excellent approach for the enhancement in the antioxidant bio-efficacy without performing synthetic structural modifications.

The exchange of information within the cell is extremely complex. Besides the well-studied chemical signalling, physical signalling is required to fulfil spatial and temporal aspects. The Golgi apparatus and the microtubule skeleton system are the decisive structures for numerous intracellular transport tasks. Close communication between the Golgi apparatus and the cell periphery is an absolute prerequisite for the well-directed positioning of structural elements. The majority of the substances that influence the cell from the membrane transmit the information to the intracellular destination via signal transduction pathways. It is discussed in detail that the transmission of information in both systems is based on emission and resonance of electromagnetic patterns in the infrared frequency range generated by the vibrations of the respective molecules. This radiation with fingerprint patterns must be coherent to activate enzymes. Coherence could be achieved by the chemical reactions of the molecules to be replaced or in the signal transduction pathways, by the phosphorylation of the transduction proteins. The quasicrystalline structure of water is essential for that coherence. The technical application of that hypothesis would open many new possibilities. However, several biological phenomena will probably only become completely explainable with the comprehensive application of modern quantum physics and there, we are at the beginning phase.

Potential Anti-diabetic Activities from Edible Bird Nest and Its Hydrolysates

Abdul Salam Babji, Azliana Abu Bakar Sajak, Nur ‘Aliah Daud, Hafeedza Abdul Rahman, Decha Sermwittayawong, Kulwanit Patninan

Current Advances in Chemistry and Biochemistry Vol. 3, 4 March 2021, Page 77-86

Traditionally, edible bird's nest (EBN) is considered as one of the delicacies, believed having numerous health benefits that been sought after in Asia, especially China. This paper discussed the potential anti-diabetic activities of the EBN and its hydrolysate. The ability of EBN hydrolysate to stimulate glucose uptake were tested by in vitro viability test using L6 myotube cells. The anti-diabetic test was done in vivo using rats, tested through fasting blood glucose and oral glucose tolerance. Metformin, the commercial drugs for anti-diabetic, was used as controls. Results showed that the dosage of 1 mg/ml of EBN hydrolysate was safe and better than metformin in the cell viability test. The findings showed that both test of glucose uptake (in vivo and in vitro) with the supplementation of EBN hydrolysate exhibited anti-diabetic activities. These results demonstrated the positive effects of hydrolysis process on EBN as an anti-diabetic agent which warrants further investigation of the EBN hydrolysate as a potential nutraceutical food supplement.

Recent Study on Copper-Promoted One-Pot Approach: Synthesis of Benzimidazoles

S. N. Murthy Boddapati, Ramana Tamminana, Ravi Kumar Gollapudi, Sharmila Nurbasha, Mohamed E. Assal, Osamah Alduhaish, Mohammed Rafiq H. Siddiqui, Hari Babu Bollikolla, Syed Farooq Adil

Current Advances in Chemistry and Biochemistry Vol. 3, 4 March 2021, Page 87-100

A facile, one-pot, and proficient method was developed for the production of various 2-arylaminobenzimidazoles. This methodology is based for the first time on a copper catalyst promoted domino C–N cross-coupling reaction for the generation of 2-arylaminobenzimidazoles. Mechanistic investigations revealed that the synthetic pathway involves a copper-based desulphurization/ nucleophilic substitution and a subsequent domino intra and intermolecular C–N cross-coupling reactions. Some of the issues typically encountered during the synthesis of 2-arylaminobezimidazoles, including the use of expensive catalytic systems and the low reactivity of bromo precursors, were addressed using this newly developed copper-catalyzed method. The reaction procedure is simple, generally with excellent substrate tolerance, and provides good to high yields of the desired products. However, the simplicity, environmental acceptability, and cost effectiveness of copper makes this method more practical.

Distribution of Proteoforms Numbers in a Human Cell according to Their Abundance is Following Zipf’s Law

Stanislav Naryzhny, Maria Maynskova, Victor Zgoda, Alexander Archakov

Current Advances in Chemistry and Biochemistry Vol. 3, 4 March 2021, Page 101-111

Human cells contain many thousands of protein components, protein species/proteoforms, whose cooperation provides the complicated functional mechanisms of the cellular proteome. Though recent methods still do not allow us to obtain the whole picture of this cooperation, they at least provide an opportunity to develop a representation of the proteome size and quantitative distribution of proteoforms inside the proteome. Using 2DE analysis followed by both protein staining and ESI LC-MS/MS analysis, we performed an analysis of the quantitative distribution of different proteoforms in human cells. We have analyzed several human cancer cell lines (HepG2, glioblastoma, MCF7) along with the primary liver cells from tissue samples and found that the dependence of the number of proteoforms on their abundance is described by Zipf's law:

y = ax-1                                                                                                                                                                                                                                                    (1),

where y stands for the number of proteoforms (N), x stands for the abundance. In the case where the abundance is expressed as %V, and a = 14, the final equation is:

N=14/%V                                                                                                                       (2).

It is highly likely that this type of distribution reflects the fundamental functional organization of the human cellular proteome since it is the same in all types of cells analyzed.

Study on Proteomic Profiling of High-grade Glioblastoma: Aspects of Biomarkers

Stanislav N. Naryzhny, Maria A. Maynskova, Victor G. Zgoda, Natalia L. Ronzhina, Svetlana E. Novikova, Natalia V. Belyakova, Olga A. Kleyst, Olga K. Legina, Rimma A. Pantina, Michael V. Filatov

Current Advances in Chemistry and Biochemistry Vol. 3, 4 March 2021, Page 112-128

Identification and quantitative analysis of different proteoforms (protein species) presented in a cell line generated from high grade glioblastoma was performed using two-dimensional electrophoresis (2DE), mass spectrometry (ESI LC-MS/MS), and immunodetection. A 2DE protein map containing an extensive data set comprising 937 spots with 1542 unique protein identifications (proteoforms) of 600 genes was obtained. Additionally, another set of experiments was performed where 16012 proteoforms coded by 4050 genes were identified by MS/MS according to their position in 96 gel sections (pixels). A special attention has been paid to the proteins that are the potential biomarkers of glioblastoma. The list of these biomarkers was compiled from literature. Next, we generated the graphs with theoretical and experimental information about proteoforms coded by the same gene. Such a virtual-experimental representation allowed better visualization of the state of these gene products. Many proteins, potential biomarkers of glioblastoma as well, are characterized by high numbers of protein species. We assume that these species could be a potential source of highly specific biomarkers of glioblastoma.

Environmental epigenetics describes how environmental factors affect cellular epigenetics and, hence, human health. Epigenetic marks alter the spatial conformation of chromatin to regulate gene expression. Environmental factors with epigenetic effects include behaviors, nutrition, and chemicals and industrial pollutants. Epigenetic mechanisms are also implicated during development in utero and at the cellular level, so environmental exposures may harm the fetus by impairing the epigenome of the developing organism to modify disease risk later in life. By contrast, bioactive food components may trigger protective epigenetic modifications throughout life, with early life nutrition being particularly important. Beyond their genetics, the overall health status of an individual may be regarded as an integration of many environmental signals starting at gestation and acting through epigenetic modifications. This review explores how the environment affects the epigenome in health and disease, with a particular focus on cancer. Understanding the molecular effects of behavior, nutrients, and pollutants might be relevant for developing preventative strategies and personalized heath programs. Furthermore, by restoring cellular differentiation, epigenetic drugs could represent a potential strategy for the treatment of many diseases including cancer. A deeper understanding of epigenetic effects and the signaling pathways activated by bioactive food components would aid in assessing the role and potential benefit of nutrients on our health and reducing cancer susceptibility.

Schiff bases are versatile ligands which are synthesized from the condensation of primary amines with carbonyl groups. These compounds are very important in medicinal and pharmaceutical fields because of their wide spectrum of biological activities. Most of them show biological activities such as antibacterial, antifungal as well as antitumor activity. Transition metal complexes derived from the Schiff base ligands with biological activity have been widely studied. This summarizes the synthesis, characterization and biological activities of Schiff bases and its transition metal complexes.