Heterocyclic Drug Design and Development
Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg in Promising Drug Molecules of Natural Origin, 2020
Depending on the carbon framework, organic compounds can be classified into the open chain and closed chain or cyclic compounds. Cyclic compounds refer to those having atoms bound to each other in the form of a ring. These cyclic compounds can be sectioned into homocyclic and heterocyclic compounds (Figure 9.2). Homocyclic compounds, also known as carbocyclic or isocyclic compounds are the ones in which ring comprises of one type of atoms, mainly carbon. In heterocyclic compounds, the ring is formed by at least two different types of atoms (including a carbon). All atoms apart from carbon that are present in a ring are known as heteroatoms. However, in the majority of compounds, a major portion of the ring is composed of carbon. Most commonly witnessed heteroatoms include nitrogen, sulfur, and oxygen (Farlex. Heterocyclic Compounds. The Free Dictionary).
A Brief Background
Nathan Keighley in Miraculous Medicines and the Chemistry of Drug Design, 2020
Reactions of organic molecules are, for the most part, governed by the presence of heteroatoms. They have the ability to disturb the electron density within the local area of the hydrocarbon skeleton and therefore create a reactive centre. The positioning and nature of the bonding of heteroatoms in organic molecules are identified as functional groups, which will undergo characteristic reactions.
Novel amides of mycophenolic acid and some heterocyclic derivatives as immunosuppressive agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Juliusz Maksymilian Walczak, Dorota Iwaszkiewicz-Grześ, Michalina Ziomkowska, Magdalena Śliwka-Kaszyńska, Mateusz Daśko, Piotr Trzonkowski, Grzegorz Cholewiński
MPA as a fully substituted aromatic compound possesses no protons in the aromatic region. This fact simplifies amides’ 1H NMR spectrum analyses since newly incorporated moieties contribute aromatic and amide protons solely. All spectra are determined by the deshielded amide proton and phenolic one as well as recently introduced aromatic species. Remaining signals represent MPA structure and are sometimes shifted due to magnetic environment modifications. Some lapping may occur as implemented amines bear functional groups or spacers appearing in the same 1H NMR regions as MPA structural units. 13C NMR spectra are also characterised by MPA core and added value in the shape of newly introduced carbon atoms. Some dissimilarities in the nucleus characteristics may occur (especially in the case of amide group carbon) as well as for amine-based units. The latter one is represented by deshielded C(2) heteroaromatic carbon and C(3a)/C(7a) positions. Remaining loci differ with heteroatom electronegativity and substituent character, sometimes precluding precise carbon atoms assignment. Some 1H and 13C NMR spectra show long and short distance spin decoupling brought by fluorine atoms, namely in A11 and A14 cases. More detailed information about the character of heteroaromatic interactions within 13C NMR spectroscopy may be found in the literature38,39.
An integrated in silico and in vivo approach to determine the effects of three commonly used surfactants sodium dodecyl sulphate, cetylpyridinium chloride and sodium laureth sulphate on growth rate and hematology in Cyprinus carpio L
Published in Toxicology Mechanisms and Methods, 2022
Ritwick Bhattacharya, Ismail Daoud, Arnab Chatterjee, Soumendranath Chatterjee, Nimai Chandra Saha
Before docking, the predicted protein files were loaded into Biovia Discovery studio for preparation steps. The steps the addition of polar hydrogen and removal of heteroatoms. Removal of water was not performed as the presence of water is essential to ensure a relay between the compound and the active site and thus create networks of hydrogen bonds (Klebe 2006). On the other hand, water molecules in the cavities of proteins can sometimes be a fundamental element as some algorithms can simulate the presence of water molecules in the cavities of proteins (Marechal 2007). Finally the minimzation of energy was performed using YASARA energy minimization server (Krieger et al. 2009) and the disputed amino acids were repaired using Molegro Virtual Docker software. The binding affinity of 3 surfactants with target protein was predicted using CB-Dock which is designed to perform docking at predicted sites, instead of the entire surface of a protein. It implements Autodoc Vina (1.12) for performing docking analysis (Liu et al. 2020). The docking pose of the ligand-protein complex was selected based on the lowest vina score and RMSD value of less than 2 Å (Liu et al. 2020). Finally, the bond type and interaction between active site residues of protein and ligand was obtained by using Protein-Ligand Interaction Profiler (PLIP) which aids in easy and fast identification of intermolecular interactions between biological macromolecules and their ligands (Salentin 2015; Adasme et al. 2021).
Acetylenes: cytochrome P450 oxidation and mechanism-based enzyme inactivation
Published in Drug Metabolism Reviews, 2019
The reactions catalyzed by cytochrome P450, with some exceptions, fall into three classes: (i) hydroxylations in which an oxygen is inserted between a hydrogen and a heavier element, usually carbon or nitrogen; (ii) heteroatom oxidations, in which the oxygen atom is added to the free electron pair of a heteroatom, usually nitrogen or sulfur; and (iii) oxidation of double, triple, or aromatic π-bonds. This review focuses exclusively on the oxidation of carbon–carbon triple bonds (i.e. acetylenic groups). The oxidation of acetylenes resembles in some, but not all respects the oxidation of olefinic bonds. The oxidation of triple bonds has appeared in general reviews on the mechanism of cytochrome P450 enzymes (e.g. Ortiz de Montellano 2015) and the mechanism-based inactivation of cytochrome P450 enzymes (e.g. Correia and Hollenberg 2015), but the last review dealing extensively with the oxidation of acetylenes was published more than 30 years ago (Ortiz de Montellano 1985). This review updates our understanding of the oxidation of acetylenes in the light of the information obtained in the quarter of a century since that last review. The discussion of the formation of metabolites and the inactivation of cytochrome P450 enzymes includes a critical reevaluation of the putative role of oxirenes as reaction intermediates, the oxidation of disubstituted triple bonds, and the nature of ‘reversible’ inhibitory complexes.