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Effects of Food Processing, Storage, and Cooking on Nutrients in Plant-Based Foods
Published in Nicole M. Farmer, Andres Victor Ardisson Korat, Cooking for Health and Disease Prevention, 2022
Polyphenols include a vast number of phytochemicals traditionally categorized into phenolic acids, stilbenes, lignans, and flavonoids. These molecules are involved in defense mechanisms against pathogens or ultraviolet radiation (Manach, Scalbert, Morand, Rémésy, & Jiménez, 2004). Polyphenols are usually classified by their structure which is determined by the number of phenol rings and the side groups attached to them (Manach et al., 2004). The flavonoid subclass of compounds includes a large group of compounds (more than 6,000) possessing two or more aromatic rings linked by an oxygenated heterocyclic bridge possessing one oxygen and three carbon atoms (Blumberg & Milbury, 2006; Manach et al., 2004). The main classes of flavonoids include anthocyanidins, flavanols, flavanones, flavones, flavonols, and isoflavones; these compounds reflect variations of the primary backbone structure (Blumberg & Milbury, 2006)
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The largest family of intercalating agents in clinical use is the anthracyclines, members of which contain four fused, aromatic rings and include the naturally occurring antibiotics doxorubicin, daunorubicin, and aclarubicin, and the related semisynthetic analogs epirubicin and idarubicin (Figure 5.43). Members of the anthracene family possess three aromatic rings, with mitoxantrone (also known as mitozantrone) and pixantrone being the main agents in common use (Figure 5.44). The third group is the phenoxazine family, members of which contain three fused, six-membered rings but with the central ring containing oxygen and nitrogen heteroatoms. The best-known member of this group is dactinomycin, which also contains two cyclic peptide side chains that stabilize the drug-DNA adduct by interacting in the minor groove of DNA (Figure 5.46). Structures of the anthracene intercalating agents mitoxantrone (NovantroneTM or OnkotroneTM) and pixantrone (PixuvriTM).
Drug Design, Synthesis, and Development
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Benzene commonly reacts with electrophiles via electrophilic substitution reactions. For example, nitration, sulfonation, and halogenation reactions, which all require a Lewis acid catalyst; an acceptor of electrons, are useful ways of introducing new functional groups to aromatic rings. Another useful example for synthesis would be the Friedel-Craft reactions (acylation and alkylation) because these form new carbon-carbon bonds, useful for combining molecular fragments.
Smart design of patient-centric long-acting products: from preclinical to marketed pipeline trends and opportunities
Published in Expert Opinion on Drug Delivery, 2022
Céline Bassand, Alessia Villois, Lucas Gianola, Grit Laue, Farshad Ramazani, Bernd Riebesehl, Manuel Sanchez-Felix, Kurt Sedo, Thomas Ullrich, Marieta Duvnjak Romic
Low solubility in body fluids can be engineered by providing high crystal lattice energy, low entropy of fusion and/or poor hydration in an aqueous environment. Rigidity (e.g. low number of rotatable bonds) and flatness of the molecular structure result in a dense packing in crystals and provide strong intermolecular bonds via van der Waals interactions, π−π stacking, or hydrogen bonding [62,63]. Poorly hydrated compounds, on the other hand, are commonly related to high lipophilicity [64]. A recent molecular study established a correlation between the number of aromatic rings in a drug molecule and its physicochemical properties. Even within a defined lipophilicity range, an increased number of aromatic rings can lead to decreased aqueous solubility [65]. For drugs designed to act in a local, confined physiological compartment – but without generating undesirably high systemic exposure (for safety reasons).
Small molecule DNA-PK inhibitors as potential cancer therapy: a patent review (2010–present)
Published in Expert Opinion on Therapeutic Patents, 2021
Suwen Hu, Zi Hui, Frédéric Lirussi, Carmen Garrido, Xiang-Yang Ye, Tian Xie
Vertex Pharma Inc. is one of the biggest players in DNA-PK inhibitor field and has published eight patents covering at least three distinct scaffolds. In its 426-page patent published in 2013, Vertex Pharma Inc. claimed a series of substituted pyrimidin-4-amines as DNA-PK inhibitors (general structure 9 in Figure 6). Ring A and Ring B are defined as aromatic rings comprising a 5- or 6-membered ring, a 5,6-fused ring or a 6,6-fused ring [56]. Of total 984 examples, representative compounds 9a-9d exhibited Ki values of less than 30 nM against DNA-PK. Interestingly, compound 9d (Example 984) was one of a few deuterated compounds listed in WO2013163190 [56]. Deuterated analog is common tactics used in medicinal chemistry to utilize the isotope effect on slowing down the metabolism. In a selection patent published in 2015 [57], Vertex Pharma Inc. claimed co-crystal form of 9e, a deuterated analog of 9a. Compound 9e (VX-984, M9831) was finally chosen as a novel drug candidate over 9d presumably due to the PK optimization. This compound potently inhibits DNA-PKcs autophosphorylation of Ser2056 in A549 lung cancer cells (IC50 = 88 nM) and has good DNA-PK selectivity over other PI3K family members [58]. VX-984 has completed a phase I clinical study in combination with PEGylated liposomal doxorubicin in patients with advanced solid tumor or lymphomas (the US clinical trial ID: NCT02644278).
Activation of Nrf2 signaling pathway by natural and synthetic chalcones: a therapeutic road map for oxidative stress
Published in Expert Review of Clinical Pharmacology, 2021
Melford Chuka Egbujor, Sarmistha Saha, Brigitta Buttari, Elisabetta Profumo, Luciano Saso
Several antioxidants have emerged as possible Nrf2 pathway activators amongst which chalcones exhibit excellent activity, having several advantages over others [10–14]. Chalcone scaffold (1,2-diphenyl-2-propen-1-one) commonly called chalconoid (Figure 1), a privileged molecule of medicinal importance, is a Michael acceptor and a precursor for the flavonoid family with therapeutic potential against several diseases [15,16]. Structurally, chalcone is made up of aromatic rings linked by α, ß-unsaturated ketone group that is linear or nearly planar in structure and this structural uniqueness accounts for its multiple biological activities [17,18]. This structure also helps chalcones to have unrestricted interactions with several proteins associated with cell apoptosis and proliferation [19,20]. Moreover, it also consists of conjugated double bonds and a delocalized π-electron system on the two aromatic rings [21]. Chalcones exhibit a broad spectrum of biological properties [22] such as antioxidant [23], anticancer [24], anti-inflammatory [25,26], antifungal [27], antimalarial [28], antitumor [29], antiprotozoal [30,31] activities. However, the effect of chalcones on Nrf2 signaling pathway activation and their recent updates need to be reviewed due to the importance of Nrf2 activation as a therapeutic target in several pathological processes mediated by oxidative stress.