Drug Design, Synthesis, and Development
Nathan Keighley in Miraculous Medicines and the Chemistry of Drug Design, 2020
Reactions of substituted benzenes depends on the functional groups already present on the ring. Regioselectivity, which governs where on the ring the reaction takes place, depends on the electronic effects of the substituents and their position on the ring. Activating groups are typically +I and +M groups, where positive induction and positive mesomeric effects donate electrons into the aromatic ring system. Deactivating groups withdraw electrons from the ring (−I and −M) and destabilise the ring, making it less reactive. Activating groups direct the reaction to the ortho and para position (depending on steric factors of the substituted benzene), while deactivating groups direct to the meta position, except for halogens, which are o/p directors. During synthesis, it is therefore important to add the substituents in the correct order to achieve the desired regioslectivity.
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).
Silicones in Cosmetics
E. Desmond Goddard, James V. Gruber in Principles of Polymer Science and Technology in Cosmetics and Personal Care, 1999
While there are many types of silicone polymers to choose from when formulating personal care products, the most commonly utilized are PDMS. This class of unmodified silicones comprise approximately of all silicone compounds found in personal care formulations, and include materials under the INCI designations of cyclomethicone, hexamethyl disiloxane, dimethicone, and dimethiconol. PDMS polymers can exist in linear structures with a degree of polymerization ranging from zero (hexamethyl disiloxane) to several thousand. Dimethylsiloxane compounds may also exist in the form of cyclic ring structures known as cyclomethicone. Currently, the term “cyclomethicone” is used to refer to all the cyclic dimethylsiloxane compounds employed in personal care formulations; however, there is an expressed desire to specify the individual materials as cyclotrisiloxane, cyclotetrasiloxane, cyclopentasiloxane, and so forth (17). Of the cyclic dimethyl fluids, ring sizes of four (referred to as octamethylcyclotetrasiloxane, , or tetramer), five (referred to as decamethylcyclopentasiloxane, , or pentamer), and six (dodecamethylcyclohexasiloxane, , or hexamer) are most frequently encountered in cosmetic products, but rings containing from three to 10 or more silicone atoms are known to exist.
Synthesis and biological evaluation of celastrol derivatives as potent antitumor agents with STAT3 inhibition
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Shaohua Xu, Ruolan Fan, Lu Wang, Weishen He, Haixia Ge, Hailan Chen, Wen Xu, Jian Zhang, Wei Xu, Yaqian Feng, Zhimin Fan
No matter the carboxyl group is protected or not, the A-ring disubstituted derivatives 2a–2g and 3a–3g had no antiproliferation effect below the maximum test concentration (12.5 μM), indicating the quinone methyl structure of celastrol is vital for activity. Significantly, celastrol was considered to affect protein function by forming covalent Michael adducts via binding to the electrophilic sites on quinone methide rings (A/B rings) of celastrol and nucleophilic thiol groups of cysteine residues25–27. It suggested us that preserving the unique quinone methyl structure of celastrol should be prioritised during structural modification. However, another two disubstituted compounds (3h and 3i, with smaller substituent groups) retain similar activity as celastrol, and the previous study28 reported similar results, which contradicts our conclusion. Therefore, the structure-activity relationship of A-ring modification needs to be further analysed.
Modulating effect of a hydroxychalcone and a novel coumarin–chalcone hybrid against mitomycin-induced genotoxicity in somatic cells of Drosophila melanogaster
Published in Drug and Chemical Toxicology, 2022
Jefferson Hollanda Véras, Camila Regina do Vale, Débora Cristina da Silva Lima, Murilo Machado dos Anjos, Aline Bernardes, Aroldo Vieira de Moraes Filho, Carolina Ribeiro e Silva, Guilherme Roberto de Oliveira, Caridad Noda Pérez, Lee Chen-Chen
Previous studies already related the antioxidant properties of coumarins with the aromatic ring (ring B) present in their structures. This ring induces a resonance in the structure and creates an electrostatic potential, which might cause this molecule to interact with ROS (Sharma et al. 2005, Barreiros et al. 2006). Furthermore, 2HMC was reported to present free radical scavenging activity 10-fold greater than other 2′-hydroxichalcones without a B-ring substituent (Kozlowski et al. 2007, Rossi et al. 2013, Das et al. 2014). Thus, the antimutagenic/antirecombinogenic effect of 2HMC and 4-MET observed in our study may be attributed, at least partially, to their high free radical scavenging capacity, which can protect DNA from the harmful actions of MMC metabolites.
Scoring rings in the cell fusion-induced premature chromosome condensation (PCC) assay for high dose radiation exposure estimation after gamma-ray exposure
Published in International Journal of Radiation Biology, 2019
Mingzhu Sun, Jayne Moquet, Stephen Barnard, David Lloyd, Elizabeth Ainsbury
PCC ring frequency can vary between scorers and has been reported with big discrepancies by different researchers due to the varying scoring criteria applied individually. The main reason is that, unlike hollow rings that have an open space in the middle, the morphology of solid rings is not easy to distinguish from small chromatid fragments and the accuracy of scoring is reduced accordingly. It should be noted that a hollow ring can further condense into a solid ring and it is only this arbitrary morphological difference that distinguishes the two types of ring. Importantly, only well condensed and well-spread lymphocytes fused with mitotic CHO cells should be scored. It has been reported (Lu et al. 2016) that the dose-response curve for solely hollow rings was a better fit than that with both hollow and solid rings albeit both curves provided the same good dose estimation for this chemical-induced PCC ring study. In some chemical-induced PCC analyses (Lamadrid et al. 2007; Balakrishnan et al. 2010), only hollow rings were scored. In the present study, the dose-response curves generated by scoring either total rings or hollow rings only showed no significant difference. On that account, it is feasible and practical to score only hollow rings in order to reduce the scoring time. Applying strict well-defined scoring criteria may be advisable for high-dose ring-based estimation to enable the inter-comparison of the results; particularly in a network of laboratories developed for emergency preparedness.
Related Knowledge Centers
- Chemistry
- Cyclic Compound
- Indole
- Pyridine
- Open-Chain Compound
- Alicyclic Compound
- Carbon
- Bicyclic Molecule
- Spiro Compound