Bitter taste in silico: A review on virtual ligand screening and characterization methods for TAS2R-bitterant interactions

León, Gerardo De; Frőhlich, Eleonore; Salar-Behzadi, Sharareh

doi:10.1016/j.ijpharm.2021.120486

Cited by 12 publications

(9 citation statements)

References 126 publications

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“…For instance, though TAS2R38 exhibits a strong bias toward recognizing thioureas N–C = S moiety (Bufe et al., 2005), not all ITCs containing this moiety exhibit bitter taste (Bell et al., 2018). In addition, the ligand‐based predictive tools have weaknesses, and the structure‐based approaches are still limited (De León et al., 2021). Thus, more profound knowledge is necessary to illustrate the relationships among the chemical structures of bitter compounds, their bitterness intensities, and the activation of TAS2Rs.…”

Section: Discussionmentioning

confidence: 99%

“…Due to their highly structurally diversities, experimental screening of bitter compounds from natural foodstuffs and medicines is often tedious and daunting (Huang et al., 2016; Zheng et al., 2018). Recently, ML‐based methods for identifying the most likely bitterants have attracted increasing attention due to their high speed, low cost, and potential for improvement as the experimental data further grow (De León et al., 2021; Margulis et al., 2022). To date, five ML‐based prediction tools have been developed, including BitterX (Huang et al., 2016), BitterPredict (Dagan‐Wiener et al., 2017), e‐Bitter (Zheng et al., 2018), BitterIntense (Margulis et al., 2021), and BitterMatch (Margulis et al., 2022).…”

Section: Bitter Taste Receptors (Tas2rs) and Bitter Signal Transductionmentioning

confidence: 99%

“…Moreover, they could provide informed suggestions for bitterness masking strategies and reduce the financial burden in the food, pharma, and biotechnology industries (Huang et al, 2016;Margulis et al, 2021Margulis et al, , 2022. However, the information in BitterDB and the complex interactions between the receptors and ligands may limit the accuracy of these ML-based predictive tools (De León et al, 2021).…”

Section: Bitter Taste Receptors (Tas2rs)mentioning

confidence: 99%

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An overview of bitter compounds in foodstuffs: Classifications, evaluation methods for sensory contribution, separation and identification techniques, and mechanism of bitter taste transduction

Yan

Hua-rong

2022

Comp Rev Food Sci Food Safe

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The bitter taste is generally considered an undesirable sensory attribute. However, bitter-tasting compounds can significantly affect the overall flavor of many foods and beverages and endow them with various beneficial effects on human health. To better understand the relationship between chemical structure and bitterness, this paper has summarized the bitter compounds in foodstuffs and classified them based on the basic skeletons. Only those bitter compounds that are confirmed by human sensory evaluation have been included in this paper. To develop food products that satisfy consumer preferences, correctly ranking the key bitter compounds in foodstuffs according to their contributions to the overall bitterness intensity is the precondition. Generally, three methods were applied to screen out the key bitter compounds in foods and beverages and evaluate their sensory contributions, including dose-over-threshold factors, taste dilution analysis, and spectrum descriptive analysis method. This paper has discussed in detail the mechanisms and applications of these three methods. Typical procedures for separating and identifying the main bitter compounds in foodstuffs have also been summarized. Additionally, the activation of human bitter taste receptors (TAS2Rs) and the mechanisms of bitter taste transduction are outlined. Ultimately, a conclusion has been drawn to highlight the current problems and propose potential directions for further research.

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Section: Discussionmentioning

confidence: 99%

Section: Bitter Taste Receptors (Tas2rs) and Bitter Signal Transductionmentioning

confidence: 99%

Section: Bitter Taste Receptors (Tas2rs)mentioning

confidence: 99%

See 1 more Smart Citation

An overview of bitter compounds in foodstuffs: Classifications, evaluation methods for sensory contribution, separation and identification techniques, and mechanism of bitter taste transduction

Yan

Hua-rong

2022

Comp Rev Food Sci Food Safe

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“…Moreover, most TCMs are liquid preparations, such as traditional Chinese oral liquid medicine and Chinese decoctions. The bitter drug molecules dissolved in water can rapidly bind to the bitter taste receptors of TAS2R10 in the oral taste buds to produce bitterness [ 31 ]. Presently, although a variety of taste-masking techniques have been reported, adding sweeteners or aromatics to trigger varied sense organs for taste masking is still the main taste-masking technique for TCMs [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

The Taste-Masking Mechanism of Chitosan at the Molecular Level on Bitter Drugs of Alkaloids and Flavonoid Glycosides from Traditional Chinese Medicine

Sun

Chen

et al. 2022

Molecules

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Taste masking of traditional Chinese medicines (TCMs) containing multiple bitter components remains an important challenge. In this study, berberine (BER) in alkaloids and phillyrin (PHI) in flavonoid glycosides, which are common bitter components in traditional Chinese medicines, were selected as model drugs. Chitosan (CS) was used to mask their unfriendly taste. Firstly, from the molecular level, we explained the taste-masking mechanism of CS on those two bitter components in detail. Based on those taste-masking mechanisms, the bitter taste of a mixture of BER and PHI was easily masked by CS in this work. The physicochemical characterization results showed the taste-masking compounds formed by CS with BER (named as BER/CS) and PHI (named as PHI/CS) were uneven in appearance. The drug binding efficiency of BER/CS and PHI/CS was 50.15 ± 2.63% and 67.10 ± 2.52%, respectively. The results of DSC, XRD, FTIR and molecular simulation further indicated that CS mainly masks the bitter taste by disturbing the binding site of bitter drugs and bitter receptors in the oral cavity via forming hydrogen bonds between its hydroxyl or amine groups and the nucleophilic groups of BER and PHI. The taste-masking evaluation results by the electronic tongue test confirmed the excellent taste-masking effects on alkaloids, flavonoid glycosides or a mixture of the two kinds of bitter components. The in vitro release as well as in vivo pharmacokinetic results suggested that the taste-masked compounds in this work could achieve rapid drug release in the gastric acid environment and did not influence the in vivo pharmacokinetic results of the drug. The taste-masking method in this work may have potential for the taste masking of traditional Chinese medicine compounds containing multiple bitter components.

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“…So, it is important to specify it toxicity with in vitro, in vivo, and / or in Silico methods. In Silico is a computational methodology predicates toxicity and other important characters with noliving species under test [7,8,9]. This computer -aided or in Silico methodology is popular approach used to evaluate chemical activity and develop or/ and candidate it to be bio-inhibitor of specific disease or bio-activator to particular biological route.…”

Section: Introductionmentioning

confidence: 99%

In Silico Taste–Toxicity Study of New Hypothetical Hetero-Abiraterone Derivatives

Khalaf¹

2022

IJOIR

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First Iraqi attempt to study drug used for prostate cancer treatment (Abiraterone) that hypothetically reacted with known chemicals classified as Anticancer drug: Tirapazamine (T) and 5-Fluorouracil (F), food additive and preservative: Butylated Hydroxy Toluene (B) and Ethoxyquin (E), and sweeteners: P-4000 (P), Sodium Cyclamate (CS), Alitame (AT), and Saccharin (SA). The second step in this work was computational study of all reactants and the formed products having newly ether, amine, and carboxylic acid ester, and sulphonate bonds by online websites. Taste, toxicity, and ADMET were calculated by three online websites related to Charite University of Medicine, Institute for Physiology, Germany and University of Melbourne, Australia. SMILES of the reactants were obtained from National Library of Medicine/ National Center for Biotechnology Information websites while products were drawn by the molecular editor CS ChemDraw Ultra and rechecked by MarvinSketch program. This in Silico study showed various results of the formed products compared to Abiraterone (A) that predicated it as sour chemical belongs to Class 4 as a harmful substance if swallowed. Abiraterone (A) toxicity on liver organ was 61% probability percentage as hepatotoxicity while carcinogenicity, Immunotoxicity, Mutagenicity, cytotoxicity, AhR, AR, Aromatase, ER, HSE, and p53 were more than 70 % to bind Progesterone or Androgen. Also, Abiraterone (A) has a poor water solubility leading to high intestinal absorption, moderate total clearance, and giving inhibition reaction to Cytochrome P450 type CYP2C19, hERG II, and Ames test. These results confirmed that Abiraterone is structurally less harmful acute class with highly chance to interact with cell components resulting lethal response. All Abiraterone hypothetical products had a harmful reaction if swelled (Class 4), sour taste. All toxicological characters may be highly affected by its water solubility and intestinal absorption towards CNS, BBB, and CaCO2 permeability, skin sensation, and Ames test issues. For example, this in Silico- QSAR foundations about Abiraterone – Saccharin (A-SA) suggest that A-SA is structurally safe and there are several possibilities of becoming an active–multiple toxicological compound.

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Bitter taste in silico: A review on virtual ligand screening and characterization methods for TAS2R-bitterant interactions

Cited by 12 publications

References 126 publications

An overview of bitter compounds in foodstuffs: Classifications, evaluation methods for sensory contribution, separation and identification techniques, and mechanism of bitter taste transduction

An overview of bitter compounds in foodstuffs: Classifications, evaluation methods for sensory contribution, separation and identification techniques, and mechanism of bitter taste transduction

The Taste-Masking Mechanism of Chitosan at the Molecular Level on Bitter Drugs of Alkaloids and Flavonoid Glycosides from Traditional Chinese Medicine

In Silico Taste–Toxicity Study of New Hypothetical Hetero-Abiraterone Derivatives

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