Chromone as a Privileged Scaffold in Drug Discovery: Recent Advances

Reis, Joana; Gaspar, Alexandra; Milhazes, Nuno; Borges, Fernanda

doi:10.1021/acs.jmedchem.6b01720

Cited by 307 publications

(180 citation statements)

References 139 publications

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“…Procyanidins, the most abundant class of proanthocyanidins found in plants [88], show no cytotoxic effects on normal cells [90], although they are able to inhibit cell proliferation and induce apoptotic death in cancer cells by increasing the ROS levels [91], decreasing the mitochondrial membrane potential and activating caspase-3 [92]. Chromones and their derivatives are heterocyclic compounds distributed throughout the plant kingdom [93] known for presenting various pharmacological activities, including antioxidant and anticancer activities, especially against multiple drug-resistant tumor cell lines [94,95]. …”

Section: Discussionmentioning

confidence: 99%

Evaluation of In Vitro Antioxidant and Anticancer Properties of the Aqueous Extract from the Stem Bark of Stryphnodendron adstringens

Baldivia

Leite

Castro

et al. 2018

IJMS

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Stryphnodendron adstringens (Mart.) Coville (Fabaceae) is a tree species native to the Brazilian Cerrado commonly known as barbatimão. In traditional medicine, decoctions or infusions of the stem bark of this plant are used in the treatment of several diseases. The objective of this study was to analyze the chemical composition of Stryphnodendron adstringens aqueous extracts (SAAE) prepared from the stem bark to assess their antioxidant activity and anticancer effects as well as characterize cell death mechanisms against murine B16F10Nex-2 melanoma cells. From the SAAE, gallic acid, gallocatechin, epigallocatechin, dimeric and trimeric proanthocyanidins mainly composed of prodelphinidin units and the isomeric chromones C-hexosyl- and O-pentosyl-5,7-dihydroxychromone were identified. The SAAE showed antioxidant activity through direct free-radical scavenging as well as through oxidative hemolysis and lipid peroxidation inhibition in human erythrocytes. Furthermore, SAAE promoted apoptosis-induced cell death in melanoma cells by increasing intracellular reactive oxygen species (ROS) levels, inducing mitochondrial membrane potential dysfunction and activating caspase-3. Together, these data show the antioxidant and anticancer effects of Stryphnodendron adstringens. These results open new perspectives for studies against other tumor cell lines and in vivo models as well as for the identification and isolation of the chemical constituents responsible for these effects.

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Section: Discussionmentioning

confidence: 99%

Evaluation of In Vitro Antioxidant and Anticancer Properties of the Aqueous Extract from the Stem Bark of Stryphnodendron adstringens

Baldivia

Leite

Castro

et al. 2018

IJMS

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“…Chromone is recognized as a privileged structure and a useful template for the design of novel compounds with potential pharmacological interest, particularly in the field of neurodegenerative, inflammatory, and infectious diseases as well as diabetes and cancer (Reis, Gaspar, Milhazes, & Borges, ). The chromone moiety (1,4‐benzopyrone), shown in Figure , is the essential component of pharmacophores of a large number of bioactive molecules (Vanguru, Merugu, Garimella, & Laxminarayana, ).…”

Section: Phenolic Compoundsmentioning

confidence: 99%

Section: Phenolic Acids-hydroxycinnamic and Hydroxybenzoic Acidsmentioning

confidence: 99%

Polyphenols: A concise overview on the chemistry, occurrence, and human health

Durazzo

Lucarini

Souto

et al. 2019

Phytotherapy Research

587

397

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This review gives an updated picture of each class of phenolic compounds and their properties. The most common classification implies the subdivision of phenolics in two main groups: flavonoids (e.g., anthocyanins, flavanols, flavanones, flavonols, flavonones, and isoflavones) and non‐flavonoids (e.g., phenolic acids, xanthones, stilbens, lignans, and tannins) polyphenols. The great interest in polyphenols is associated with their high potential application for food preservation and for therapeutic beneficial use. The relationship between polyphenol intake and human health has been exploited with special reference to cardiovascular diseases, hypertension, diabetes, metabolic syndrome, obesity, and cancer. The use of current existing databases of bioactive compounds including polyphenols is described as key tools for human health research.

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“…Studies have identified various scaffolds or core structures that have privileged characteristics in terms of the activity of a certain target. 49,50,51 Core structure selection is the starting point in a scaffold-based drug discovery. Choosing or designing a proper initial scaffold is never trivial, and medicinal chemists may need enough experience to get such a skill.…”

Section: Core Selectionmentioning

confidence: 99%

AI-aided design of novel targeted covalent inhibitors against SARS-CoV-2

Tang

Liu

et al. 2020

Preprint

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The focused drug repurposing of known approved drugs (such as lopinavir/ritonavir) has been reported failed for curing SARS-CoV-2 infected patients. It is urgent to generate new chemical entities against this virus. As a key enzyme in the life-cycle of coronavirus, the 3C-like main protease (3CL pro or M pro ) is the most attractive for antiviral drug design. Based on a recently solved structure (PDB ID: 6LU7), we developed a novel advanced deep Q-learning network with the fragment-based drug design (ADQN-FBDD) for generating potential lead compounds targeting SARS-CoV-2 3CL pro . We obtained a series of derivatives from those lead compounds by our structure-based optimization policy (SBOP). All the 47 lead compounds directly from our AI-model and related derivatives based on SBOP are accessible in our molecular library at https://github.com/tbwxmu/2019-nCov. These compounds can be used as potential candidates for researchers in their development of drugs against SARS-CoV-2.author/funder. All rights reserved. No reuse allowed without permission. : bioRxiv preprint disease (COVID-19) worldwide. 1 As of March 2, 2020, more than 90,000 people have been infected by SARS-CoV-2 and more than 3000 people have been reported dead according to Johns Hopkins Coronavirus map tracker. 2 The numbers of infection and death are still increasing. To face the considerable threat of SARS-CoV-2, it is urgent to develop new inhibitors or drugs against this deadly virus. Unfortunately, since the outbreak of severe acute respiratory syndrome (SARS) eighteen years ago, there has been no approved treatment against the SARS coronavirus (SARS-CoV), 3 which is similar to SARS-CoV-2. Repurposing potential drugs such as lopinavir and ritonavir also failed to SARS-CoV-2 injected patients. 4 Structure-based antiviral drug design with a new artificial intelligence algorithm may represent a more helpful approach to get the SARS-CoV-2 targeted inhibitors or drugs. Thanks to the prompt efforts of many researchers, we have several pieces of important information about this vital virus genome and protein structures. We now know that the non-structural protein 5 (Nsp5) is the main protease (M pro ) of SARS-CoV-2 and it is a cysteine protease, which also been called "3C-like protease" (3CL pro ). Moreover, we know that the 3D structure of 3CL pro is very similar to SARS-CoV with a sequence identity of >96% and 3D structure superposition RMSDCα of 0.44 Å as shown in Figures S1 and S2. 3CL pro has been reported as an attractive target for developing anti-coronaviral drugs: 1) this protease is highly conserved in both sequences and 3D structures; 5 2) 3CL pro is a key enzyme for related virus (including SARS and SARS-CoV-2) replication; 3) it only exists in the virus, not in humans. Developing specific antiviral drugs targeting 3CL pro of the specific virus has shown significant success; for example, both approved drugs lopinavir and ritonavir can completely occupy the substrate-binding site of 3CL pro to break down the replication of human immunodeficien...

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Chromone as a Privileged Scaffold in Drug Discovery: Recent Advances

Cited by 307 publications

References 139 publications

Evaluation of In Vitro Antioxidant and Anticancer Properties of the Aqueous Extract from the Stem Bark of Stryphnodendron adstringens

Evaluation of In Vitro Antioxidant and Anticancer Properties of the Aqueous Extract from the Stem Bark of Stryphnodendron adstringens

Polyphenols: A concise overview on the chemistry, occurrence, and human health

AI-aided design of novel targeted covalent inhibitors against SARS-CoV-2

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