China
Africa
Explore chapters and articles related to this topic
Introduction
Published in Brijesh Kumar, Vikas Bajpai, Vikaskumar Gond, Subhashis Pal, Naibedya Chattopadhyay, Phytochemistry of Plants of Genus Cassia, 2021
Brijesh Kumar, Vikas Bajpai, Vikaskumar Gond, Subhashis Pal, Naibedya Chattopadhyay
In the seed extract of C. occidentalis chrysophanol, toxins, 1,4-oxazine derivative n-methyl morpholine has been isolated. Seeds also contain physcion, physciondianthron heterosides and physcion condensed as homodianthrone as well as a mixture of anthraquinones. 1-glucoside of physcion (0.018%) along with physcion (0.0068%) and two new anthraquinones like 1, 8-dihydroxy-2-methyl anthraquinone (0.0014%) and 1,4,5-trihydroxy-3-methyl-7-methoxy anthraquinone (0.0016%), chrysophanol free and as a glycoside were also found in seed samples. A new polysaccharide galactomannan consisting of d-galactose and d-mannose in the proportion of 1:3.1, as well as trace amount of d-xylose was also found in the C. occidentalis seeds. Maltose, lactose, sucrose and raffinose are also detected from seed. Some other compounds identified from the seeds of C. occidentalis are -1,8-dihydroxy-2-methyl anthraquinone, physcion, rhein, aloe-emodin, chrysophanol and steroidal glucosides. An analysis of flowers indicated the presence of anthraquinones, emodin, physcion and physcion-1-O-β-d-glucoside as well as the ubiquitous sterol β-sitosterol (Veerachari and Bopaiah, 2012).
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
While Morpholinos contain standard nucleic acid bases, they are bound to morpholine rings instead of the deoxyribose rings as in DNA, and are linked through phosphorodiamidate instead of phosphates groups. Crucially, replacement of anionic phosphates with the uncharged phosphorodiamidate groups eliminates ionization in the usual physiological pH range, so Morpholinos remain uncharged at physiological pH in cells or whole organisms. Due to their unnatural backbones, Morpholinos are not recognized by cellular proteins, thus nucleases do not degrade Morpholinos, nor are they degraded in serum or in cells. Furthermore, they do not activate toll-like receptors and so do not activate innate immune responses such as interferon induction or the NF-κB mediated inflammation response.
Biocatalysts: The Different Classes and Applications for Synthesis of APIs
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Using hydroxynitrile lyases (HNLs) Ritzen et al. (2010) prepared cis- and trans-2,5-disubstituted morpholines; their structural motif is widespread in biologically active and pharmaceutical compounds—examples are Gefitinib, an EGFR inhibitor, used for the treatment of various cancers, the antibiotic Linezolid (treatment of infections), or the strong opioid analgesic dextromoramide. Morpholine structural elements are also found in a variety of agrochemical fungicides and bactericides.
Antisense Oligonucleotide Therapy for Ophthalmic Conditions
Published in Seminars in Ophthalmology, 2021
Kevin Ferenchak, Iris Deitch, Rachel Huckfeldt
The phosphodiester backbone of single-stranded RNA and AON can easily degrade in a cell, which limited the practical applications of antisense therapy for many years. Since they were first described, modifications have developed, which make AON viable in vivo with a longer half-life, more resistant to degradation, and more likely to be taken up by cells. These modifications include changes such as the first generation phosphorothioate (PS) backbone, which improved nuclear uptake.23 A phosphoramidate morpholino has been investigated to improve stability, but its viability may be limited by quicker clearance.24,25 Common second generation modifications are a 2ʹO-methoxy ethyl (2MOE) or 2ʹO-methyl (2OME) group attached to the sugar residues of the PS backbone, which further increase stability and cellular uptake.26,27
Morpholine-based chalcones as dual-acting monoamine oxidase-B and acetylcholinesterase inhibitors: synthesis and biochemical investigations
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Rani Sasidharan, Bo Hyun Eom, Jeong Hyun Heo, Jong Eun Park, Mohamed A. Abdelgawad, Arafa Musa, Nicola Gambacorta, Orazio Nicolotti, Sreedharannair Leelabaiamma Manju, Bijo Mathew, Hoon Kim
Morpholine is a tetrahydro-1,4-oxazine with a saturated heterocyclic ring and provides a promising developmental starting point due to its biological profile with metabolic stability. The presence of a heteroatom like oxygen or nitrogen facilitates hydrogen bonding, and thus, interactions with enzymes, and the presence of electron-deficient atoms may also impart hydrophobic interactions with morpholine. From the synthetic perspective, various molecular scaffolds have been added to morpholine by replacing its secondary nitrogen11. Moclobemide (1) and reboxetine (2) (both antidepressants) provide examples of FDA-approved drugs containing the morpholine moiety (Figure 1). These drugs reversibly inhibit MAO-A and selectively inhibit norepinephrine reuptake in the central nervous system (CNS), and thus, block the human a4b2 nicotinic acetylcholine receptor. In addition, more than 20 drugs containing the morpholine moiety have been FDA approved; they include mycophenolate mofetil (an immunosuppressant), linezolid and finafloxacin (antibiotics), geftinib (an antineoplastic and epidermal growth factor inhibitor), rivaroxaban (an anticoagulant and factor Xa inhibitor), and eteplirsen, which is used to treat Duchenne muscular dystrophy12. Considering the importance of morpholine nucleus, it is worthwhile to design morpholine derived compounds of medicinal chemistry interest.
Challenging inflammatory process at molecular, cellular and in vivo levels via some new pyrazolyl thiazolones
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Perihan A. Elzahhar, Rana A. Alaaeddine, Rasha Nassra, Azza Ismail, Hala F. Labib, Mohamed G. Temraz, Ahmed S. F. Belal, Ahmed F. El-Yazbi
Regarding thiazolones (1 and 2) originating from 5-chloropyrazole-aldehyde (a), the piperidino-derivative 1 showed 1.7 times the activity of quercetin towards 15-LOX inhibition. Switching to the morpholino analogue 2 slightly decreased 15-LOX inhibitory activity but still spanning within the same order of magnitude. Concerning thiazolones (3 and 4) derived from 1,3-diphenyl pyrazole-aldehyde (b), piperidine derivative 3 demonstrated higher 15-LOX inhibition that somewhat decreased upon replacement with morpholine moiety, yet, retaining the same one-digit micromolar range of inhibition. As for thiazolones (5 and 6) obtained from 1-phenyl-3-p-tolyl pyrazole-aldehyde (c), the lowest activity for 15-LOX inhibition was noticed with the piperidine derivative 5. Enhancement of activity occurred upon switching to the morpholino-analogue 6, showing IC50 value of 2.85 μM for 15-LOX inhibition. While in case of the thiazolones (7 and 8) bearing an EDG methoxy group on the pyrazole-aldehyde moiety, the piperidine analogue 7 was almost equipotent to quercetin for 15-LOX inhibition but the activity decreased upon shifting to the morpholine derivative 8. Finally, the thiazolones (9 and 10) carrying bromo substituent on the pyrazole-aldehyde moiety had 15-LOX inhibitory activities corresponding to 59% and 74% of the activity of quercetin, respectively.