The use of the Klopman index as a new descriptor for pharmacophore analysis on strong aromatase inhibitor flavonoids against estrogen-dependent breast cancer

Kızılcan, Dilek Şeyma; Türkmenoğlu, Burçin; Güzel, Yahya

doi:10.1007/s11224-020-01498-9

Cited by 11 publications

(11 citation statements)

References 27 publications

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“…All 4 tested molecules had log P < 5, a criterion for a good drug candidate. The molecular frontier orbitals are important descriptors related to the reactivity of molecules and therefore center to explore ligandreceptor interactions [35,36]. The HOMO energy is linked to the tendency of a molecule to donate electrons to empty molecular orbitals of partner molecules.…”

Section: Resultsmentioning

confidence: 99%

Eugenol and Other Vanilloids Hamper Caenorhabditis elegans Response to Noxious Heat

2020

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Eugenol, a known vanilloid, was frequently used in dentistry as a local analgesic in addition, antibacterial and neuroprotective effects were also reported. Eugenol, capsaicin and many vanilloids are interacting with the transient receptor potential vanilloid 1 (TRPV1) in mammals and are activated by noxious heat. The pharmacological manipulation of the TRPV1 has been shown to have therapeutic value. Caenorhabditis elegans (C. elegans) express TRPV orthologs (e.g. OCR-2, OSM-9) and it is a commonly used animal model system to study nociception as it displays a well-defined and reproducible nocifensive behavior. After exposure to vanilloid solutions, C. elegans wild type (N2) and mutants were placed on petri dishes divided in quadrants for heat stimulation.Thermal avoidance index was used to phenotype each tested C. elegans experimental groups. The results showed that eugenol, vanillin and zingerone can hamper nocifensive response of C. elegans to noxious heat (32°C -35°C) following a sustained exposition. Also, the effect was reversed 6h post exposition. Furthermore, eugenol and vanillin did not target specifically the OCR-2 or OSM-9 but zingerone did specifically target the OCR-2 similarly to capsaicin. Further structural and physicochemical analyses were performed. Key parameters for quantitative structure-property relationships (QSPR), quantitative structure-activity relationships (QSAR) and frontier orbital analyses suggest similarities and dissimilarities amongst the tested vanilloids and capsaicin in accordance with the relative anti-nociceptive effects observed.

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Section: Resultsmentioning

confidence: 99%

Eugenol and Other Vanilloids Hamper Caenorhabditis elegans Response to Noxious Heat

2020

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Section: Resultsmentioning

confidence: 99%

Vanilloids HamperCaenorhabditis elegansResponse to Noxious Heat

Nkambeu

Salem

Beaudry

2020

Preprint

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Eugenol, a known vanilloid, was frequently used in dentistry as a local analgesic in addition, antibacterial and neuroprotective effects were also reported. Eugenol, capsaicin and many vanilloids are interacting with the transient receptor potential vanilloid 1 (TRPV1) in mammals and are activated by noxious heat. The pharmacological manipulation of the TRPV1 has been shown to have therapeutic value. Caenorhabditis elegans (C. elegans) express TRPV orthologs (e.g. OCR-2, OSM-9) and it is a commonly used animal model system to study nociception as it displays a well-defined and reproducible nocifensive behavior. After exposition to vanilloid solutions, C. elegans wild type (N2) and mutants were placed on petri dishes divided in quadrants for heat stimulation. Thermal avoidance index was used to phenotype each tested C. elegans experimental groups. The results showed that eugenol, vanillin and zingerone can hamper nocifensive response of C. elegans to noxious heat (32°C – 35°C) following a sustained exposition. Also, the effect was reversed 6h post exposition. Furthermore, eugenol and vanillin did not target specifically the OCR-2 or OSM-9 but zingerone did specifically target the OCR-2 similarly to capsaicin. Further structural and physicochemical analyses were performed. Key parameters for quantitative structure-property relationships (QSPR), quantitative structure-activity relationships (QSAR) and frontier orbital analyses suggest similarities and dissimilarities amongst the tested vanilloids and capsaicin in accordance with the relative anti-nociceptive effects observed.

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“…flavonoids, phenolics, stilbenes, alkaloids, terpenes, and sterols). Phenolics and flavonoids were the most represented class (63.5%) as they has been reported previously to be HA-specific inhibitors [13][14][15] and they are also considered the most abundant metabolites among other plant natural products.…”

Section: Introductionmentioning

confidence: 81%

“…Plant-based natural products are still a crucial and diverse source of potential therapeutics and nutraceuticals that have a good safety profile. Many plant-derived compounds have been reported as very good ArIs, particularly, flavonoids and other phenolic compounds 12,15 . However, their exact molecular interaction remained to be explored.…”

Section: Discussionmentioning

confidence: 99%

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Targeting allosteric sites of human aromatase: a comprehensive in-silico and in-vitro workflow to find potential plant-based anti-breast cancer therapeutics

Alhadrami

Sayed

Melebari

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Recent findings suggested several allosteric pockets on human aromatase that could be utilised for the development of new modulators able to inhibit this enzyme in a new mechanism. Herein, we applied an integrated in-silico-based approach supported by in-vitro enzyme-based and cell-based validation assays to select the best leads able to target these allosteric binding sites from a small library of plant-derived natural products. Chrysin, apigenin, and resveratrol were found to be the best inhibitors targeting the enzyme's substrate access channel and were able to produce a competitive inhibition with IC 50 values ranged from 1.7 to 15.8 mM. Moreover, they showed a more potent antiproliferative effect against ERþ (MCF-7) than ER-one (MDA-MB-231) cell lines. On the other hand, both pomiferin and berberine were the best hits for the enzyme's haem-proximal cavity producing a non-competitive inhibition (IC 50 15.1 and 21.4 mM, respectively) and showed selective antiproliferative activity towards MCF-7 cell lines.

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The use of the Klopman index as a new descriptor for pharmacophore analysis on strong aromatase inhibitor flavonoids against estrogen-dependent breast cancer

Cited by 11 publications

References 27 publications

Eugenol and Other Vanilloids Hamper Caenorhabditis elegans Response to Noxious Heat

Eugenol and Other Vanilloids Hamper Caenorhabditis elegans Response to Noxious Heat

Vanilloids HamperCaenorhabditis elegansResponse to Noxious Heat

Targeting allosteric sites of human aromatase: a comprehensive in-silico and in-vitro workflow to find potential plant-based anti-breast cancer therapeutics

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