Sparking and Sustaining the Essential Functions of Research
Thomas S. Inui, Richard M. Frankel in Enhancing the Professional Culture of Academic Health Science Centers, 2022
Kekulé later described his discovery of the ring structure of benzene as having occurred to him in a dream. He had been working on the problem for many years, without success. Then one day he was sitting by the fire, daydreaming, when before his eyes appeared a pair of serpents. The serpents opened their mouths and caught each other’s tails, creating a ring. This led Kekulé to the sudden realization that benzene might be hexagonal. The structure had never appeared on the chalkboards of chemists who had been trying to deduce it by the laws of logic, and it was utterly unlike anything else in chemistry. In this remarkable anecdote, Kekulé reveals that science does not always progress strictly by the link-by-link construction of chains of logic. In many cases, what is needed is a moment of inspiration, a sudden burst of insight whose timing is hard to predict and whose source is impossible to pinpoint. Above all, what is needed is the capacity to dream.
HIV Integrase Inhibitors
Satya Prakash Gupta in Cancer-Causing Viruses and Their Inhibitors, 2014
Vengurlekar et al. (2010) reported a 2Dand 3D-QSAR study on 24 benzyl amide-keto acids using a SAR dataset that measured strand transfer inhibition (Walker et al. 2007). These 2D-QSAR models were developed using MLR, PLS, and PCR with stepwise variable selection. The models were validated using leave-one-out cross validation. Of the three 2D-QSAR models, the MLR model was the most optimal. The descriptors in the 2D-QSAR model indicate high dipole, polarizability, and hydrogen count contribute positively to the biological activity. An MFA-based 3D-QSAR study on this dataset was also performed by these authors. Contour plots of the KNN-MFA 3D-QSAR model indicated that freedom of an amide C-N bond as opposed to an acyclic C-C bond is required for biological activity. In addition, the authors mentioned that the presence of less bulky groups on the benzene ring would lead to favorable activity. These results complement the results of the 2D-QSAR study.
Radiometry
Michael Ljungberg in Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Organic scintillators usually contain aromatic carbon compounds, consisting of carbon and hydrogen. In these compounds, the carbon atoms form benzene rings, each containing six carbon atoms and a carbon atom in the ring is thus bound to two carbon atoms and one hydrogen atom. This molecule is planar, that is, the orbitals of the bound electrons all lie in the same plane with a bond angle of 120°. However, one of the electrons in the carbon L-shell does not take part in the bonds, and these six electrons form orbitals that are orthogonal to the molecular plane. These π-electrons make it possible for the benzene molecule to bind to another benzene molecule. Absorption of energy may cause excitation of a π-electron, followed by emission of light upon de-excitation.
N-monoarylacetothioureas as potent urease inhibitors: synthesis, SAR, and biological evaluation
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Wei-Yi Li, Wei-Wei Ni, Ya-Xi Ye, Hai-Lian Fang, Xing-Ming Pan, Jie-Ling He, Tian-Li Zhou, Juan Yi, Shan-Shan Liu, Mi Zhou, Zhu-Ping Xiao, Hai-Liang Zhu
With the aim to explore the structural determinants of the guidance for further SAR studies, molecular docking of the most potent inhibitor b19 into urea binding site was performed, and the binding model is depicted in Figure 4. This model revealed that the monosubstituted thiourea moiety is nicely bound to urea binding site (Figure 4(A)), and is of primary importance for its network of interactions (Figure 4(B)): it coordinates the nickel ion and establishes hydrogen bonds with N of His138, O of Asn168, and Me of Ala365, respectively. On the other hand, the benzene ring of b19 establishes appropriate hydrophobic contacts with the hydrophobic gap (Met317, Leu318, and Met366) under the movable flap, a helix-turn-helix motif composed of residues α313–α346. Moreover, benzene ring is further solid by an S–H···π with Cys321, and a C–H···N with Leu318. In addition, this model also suggested that the aceto moiety as a donor as well as an acceptor forms C–H···N and N–H···O hydrogen bonds with His322 and Arg338, respectively. The enzyme assay data and the molecular docking results indicated that compound b19 is a potential inhibitor of urease.
Pharmacophore-based discovery of 2-(phenylamino)aceto-hydrazides as potent eosinophil peroxidase (EPO) inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Daniela Schuster, Martina Zederbauer, Thierry Langer, Andreas Kubin, Paul G. Furtmüller
In order to obtain more detailed information, we analysed the dependence of the position and the substituents on benzene ring (Table 4). From the analysis of the IC50 values it becomes clear that substituents in position 4 play an important role. The highest inhibitory activity can be found if chlorine is in this position, followed by fluorine and iodine, whereas bromine shows the lowest activity. If position 4 is free, or there is a methyl group, the amino-aceto-hydrazide shows very weak inhibitory effect compared to the halides substituents. The lowest IC50 values can be found when fluorine is in position 2 or if two fluorine atoms occupy position 2 and 4. A similar IC50 value was measured with the mixed halide, when chlorine was in position 3 and fluorine in position 4. Less important positions are position 6 and position 3, if they are occupied with one halide.
Linalool reverses benzene-induced cytotoxicity, oxidative stress and lysosomal/mitochondrial damages in human lymphocytes
Published in Drug and Chemical Toxicology, 2022
Ahmad Salimi, Farzad Khodaparast, Shahab Bohlooli, Niloufar Hashemidanesh, Elahe Baghal, Lotfollah Rezagholizadeh
Benzene with chemical formula C6H6 is used as a solvent and chemical intermediate extensively in the industrial processes. Benzene has categorized as a group 1 carcinogen in animals and human by The International Agency for Research of Cancer (IARC) (Bahadar et al. 2014). The main sources for human exposure with benzene are occupational exposure, gasoline vapor, cigarette smoke, vehicle emissions, and soil or water contaminated with benzene (Weisel 2010). The humans are exposed to this agent via the inhalation of vapors released by cigarette smoke, service stations and motor vehicles (Schnatter et al. 2005). Also, contamination can happen due to the ingestion of polluted water or foods (Schnatter et al. 2005). A great number of industrial settings, such as rubber production plants and refineries, shoe manufacturing and printing factories as well as the main sources for exposure with benzene through occupational activities (Duarte-Davidson et al. 2001). Among of above sources cigarette smoke and gasoline are two main sources of exposure to benzene. Smokers take in about 10 times more benzene than nonsmokers each day (Weisel 2010). Therefore, human population are inevitably subjected to benzene both in occupational and environmental settings, and this demonstrates a critical concern for public health (De Donno et al. 2018).
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