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Herbal Drug Discovery Against Inflammation: From Traditional Wisdom to Modern Therapeutics
Published in Amit Baran Sharangi, K. V. Peter, Medicinal Plants, 2023
Shalini Dixit, Karuna Shanker, Madhumita Srivastava, Priyanka Maurya, Nupur Srivastava, Jyotshna, Dnyaneshwar U. Bawankule
A polyphenolic compound hydroxytyrosol, from extra virgin olive oil, exhibits strong anti-inflammatory activity by improvement in a model of DSS-induced colitis (Sánchez et al., 2015). Resveratrol mainly present in grapes, wine, and peanut products, etc., is a polyphenolic stilbene which occurs in cis or trans configuration. Laboratory studies on animals, human cultured cells suggest that it possess therapeutic potential as anti-inflammatory, anti-carcinogenic, anti-oxidants which may further prove relevant for the treatment of chronic diseases (Smoliga, Baur, and Hausenblas, 2011). Another important flavonol, kaempferol [3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one] has a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anticancer, cardioprotective, neuroprotective, antiallergic, and antidiabetic (Somani et al., 2015).
Dietary Isoflavones-Mechanism and Efficacy in Cancer Prevention and Treatment
Published in Sheeba Varghese Gupta, Yashwant V. Pathak, Advances in Nutraceutical Applications in Cancer, 2019
Richa Dayaramani, Jayvadan K. Patel
Chemically, they are heterocyclic compounds having a chemical name as 3-phenyl-4H-chrome-4-one or 4H-1-benzopyran-4-one. They differ from flavones in the location of the phenyl group, which is found attached to the second carbon in the latter. Their molecular formula is C15H10O2 and molecular weight is 222.243 g/mol. The basic structure of isoflavone is shown in Figure 15.3.
Pharmacological Treatment of Lymph Stasis
Published in Waldemar L. Olszewski, Lymph Stasis: Pathophysiology, Diagnosis and Treatment, 2019
The benzopyrones represent a very effective pharmacological means of treating acute and chronic forms of high protein edema including primary and secondary forms of lymphedema. Their effectiveness is not only related to the dose but also to the type of benzopyrone used. The most efficacious benzopyrone investigated to date has been coumarin administered as 200 mg/d. Under such a regimen a patient with a long-standing lymphostatic disorder can expect subjective improvements in bursting pains, tightness, tension, heaviness, and mobility of the extremity within 4 weeks. There will be a softening of the tissues (assessed by tonometry) which can be objectively measured within 8 weeks and a reduction in the circumference and volume of edema fluid of the limb within 6 months. All of these mean a better quality of survival for the patient. For patients with acute lymphostatic disorders through thermal wounding, traumatic damage, or surgical intervention, there can be a reduction in the amount of edema fluid accumulation and associated pain. While the necessary detailed clinical trials have not been pursued, experimental work indicates the benzopyrones to be very useful prophylactically when surgical intervention of any type is anticipated.
Natural compounds as inhibitors of transthyretin amyloidosis and neuroprotective agents: analysis of structural data for future drug design
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Lidia Ciccone, Nicoló Tonali, Susanna Nencetti, Elisabetta Orlandini
By comparing the molecular structure of γ-M and T4, it is possible to note the similarity of γ-M with the endogenous ligand, in particular, the two aromatic rings and the dimethylallyl group which superpose exactly with the T4 structure (Figure 7(A)). At the same time, it is possible to recognise the benzopyran ring typical of flavonoids. This can let hypothesise a similar binding affinity for the TTR. γ-M is an effective inhibitor against the amyloid fibril formation of V30M amyloidogenic TTR. In vitro binding assays by fluorescence spectroscopy, pull-down assay using CN-Br activated Sepharose, ANS competitive test, and cross-linking followed by SDS-PAGE, revealed that γ-M is the most potent of the all tested xanthone derivatives (IC50=7 µM), and it binds to the T4-BS and stabilises the TTR tetramer54.
Novel approaches to the discovery of selective human monoamine oxidase-B inhibitors: is there room for improvement?
Published in Expert Opinion on Drug Discovery, 2019
Paolo Guglielmi, Simone Carradori, Alessandra Ammazzalorso, Daniela Secci
The reduction of the imine bond did not give univocal results; the simultaneous presence of methyl groups or a methyl along with chlorine atom bound, respectively, at the C4 and C3 of the coumarin ring were well-tolerated. The substitution of the oxygen atom of benzopyran ring with the nitrogen one had a detrimental effect, regardless the imine/amine bond. The most active compound against hMAO-B exhibited the ability to inhibit Aβ1-42 aggregation and was endowed with good chemical-physical properties, being able to cross the BBB. Docking studies placed the coumarin moiety within the substrate cavity in close proximity of the FAD and the carbonyl group of lactone system establishing hydrogen bond with Tyr435. Besides, the phenyl ring bound to the C7 was directed toward the hydrophobic pocket in the entrance cavity, establishing hydrophobic interactions and accounting for the beneficial effect of lipophilic group at the para position of the phenyl ring.
The role of cancer stem cells and the therapeutic potential of TRX-E-002-1 in ovarian cancer
Published in Expert Opinion on Orphan Drugs, 2018
Muhammad Saif, E. I. Ager, Penelope Field, K. J. Lilischkis
The benzopyran (BP) pharmacophore, at the core of TRX-E-002–1, has provided fertile ground for oncology drug candidates (Table 3). Chemical optimization has resulted in three generations of BP molecules. First generation BP compounds showed promise in clinical trials but were limited by poor bioavailability [70–73]. Of the second generation benzopyrans, ME-344 remains under clinical investigation [74–76]. A third generation of BPs, which includes trilexium (TRX-E-009–1) and TRX-E-002–1, has now been developed, with the latter currently under assessment in a phase 1 trial (Table 3) [77]. Preclinical studies indicate that with each generation, a progressive increase in anticancer activity has been achieved and that third-generation benzopyran compounds are not only cytotoxic to differentiated cancer cells but undifferentiated/stem-like cancer cells [10,62,63,78–83]. Moreover, successive rounds of chemical modification have selected for different mechanisms of actions, reflecting the pleiotropic nature of the pharmacophore [62,63,78–83]. The increase in anticancer potency likely reflects changes in the predominant mode of action. Given the lack of current clinical data confirming a role for CSCs, it is also important to note significant preclinical evidence that the third-generation benzopyran, TRX-E-002–1 is active against non-CSC cells (in addition to CSCs) [68]. This non-CSC activity ensures that there is potential for patient benefit even in the absence of a significant effect on (or role for) CSC in EOC. TRX-E-002–1 was developed for IP delivery based on current evidence of a potential survival advantage to regimes that contain an IP component to cytotoxic chemotherapy for this patient population.