tLyp–1: A peptide suitable to target NRP–1 receptor

Larue, Ludivine; Kenzhebayeva, Bibigul; Al-Thiabat, Mohammad Gasem; Jouan–Hureaux, Valérie; Mohd–Gazzali, Amirah; Wahab, Habibah A.; Boura, Cédric; Yeligbayeva, Gulzhakhan; Nakan, Ulantay; Frochot, Céline; Acherar, Samir

doi:10.1016/j.bioorg.2022.106200

Cited by 8 publications

(7 citation statements)

References 64 publications

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“…Drugs with low protein binding may have a high therapeutic index [60]. Another well-known parameter is the Blood-Brain Barrier (BBB), which facilitates the selective transfer of drug molecules between the blood and the brain parenchyma [48,60,67]. As predicted, eurycomanone and eurycomalactone were not able to cross the BBB as compared to methotrexate, which adds to the safety profile of these compounds.…”

Section: Lipinski's Rule and Admet Of Eurycomanone And Eurycomalactonementioning

confidence: 94%

“…The resulting score energies were −7.93 kcal/mol and −8.19 kcal/mol, respectively, with small root mean square deviations (RMSDs) of 0.98 Å for TNF-α and 0.62 Å for DHFR (Table 5). An RMSD value of ≤ 2.0 Å is typically considered acceptable in the literature [45][46][47][48][49]. Based on these results, we applied the same docking parameters to dock eurycomanone and eurycomalactone.…”

Section: Molecular Docking Analysismentioning

confidence: 99%

“…Caco-2 permeability is an important parameter when determining oral absorption and permeability in the early stages of drug development, and the ideal value is greater than −5.15 cm/s [48,61]. Eurycomanone and methotrexate showed low permeability, while eurycomalactone displayed higher permeability compared to the rest.…”

Section: Lipinski's Rule and Admet Of Eurycomanone And Eurycomalactonementioning

confidence: 99%

“…To the best of our knowledge, there are no in vitro or in vivo studies being reported on pharmacokinetic properties on eurycomalactone. Eurycomanone, eurycomalactone and methotrexate all showed high levels of human intestinal absorption satisfaction (HIA% with a value of 30%), which is a crucial parameter associated with human intestinal absorption [48,65], affecting the way compounds pass through biological membranes under the influence of physicochemical properties. In the body, plasma protein binding plays a significant role in the dynamics of compounds [60,66].…”

Section: Lipinski's Rule and Admet Of Eurycomanone And Eurycomalactonementioning

confidence: 99%

“…Short half-time periods and low clearance rates were predicted from our study for eurycomanone, eurycomalactone, and methotrexate. As a leading cause of drug withdrawals from the market, drug-induced toxicity will remain a key concern for the development of novel molecules [46,48,72]. Eurycomanone and eurycomalactone showed low risk in exerting hepatotoxicity and carcinogenicity effects, whereas eurycomalactone had lower risk in exerting mutagenicity effect as compared to eurycomanone.…”

Section: Lipinski's Rule and Admet Of Eurycomanone And Eurycomalactonementioning

confidence: 99%

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In Vitro and In Silico Analysis of the Anti-cancer Effects of Eurycomanone and Eurycomalactone from <em>Eurycoma longifolia.</em>

Yunos¹,

Wahab²,

Al-Thiabat³

et al. 2023

Preprint

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Eurycomanone and eurycomalactone are known quassinoids present in the roots and stems of Eurycoma longifolia. These compounds had been reported to have cytotoxic effects, however, their mechanism of action in a few cancer cell lines have yet to be elucidated. This study was aimed to investigate the anti-cancer effects and mechanisms of action of eurycomanone and eurycomalactone in cervical (HeLa), colorectal (HT29) and ovarian (A2780) cancer cell lines via Sulforhodamine B assay. Their mechanism of cell death was evaluated based on Hoechst 33342 assay and in silico molecular docking toward DHFR and TNF-α as putative protein targets. Eurycomanone and eurycomalactone exhibited in vitro anti-cancer effects manifesting IC50 values of 4.58 ± 0.090 µM and 1.60 ± 0.12 µM (HeLa), 1.22 ± 0.11 µM and 2.21 ± 0.049 µM (HT-29), and 1.37 ± 0.13 µM and 2.46 ± 0.081 µM (A2780) respectively. They induced apoptotic cancer cell death in dose- and time-dependent manners. Both eurycomanone and eurycomalactone were also predicted to have good inhibitory potential as demonstrated by the docking into TNF-α with binding affinity of -8.83 and -7.51 kcal/mol, respectively, as well as into DHFR with binding affinity results of -8.05 and -8.87 kcal/mol, respectively. These results support the evidence of eurycomanone and eurycomalactone as anti-cancer agents via apoptotic cell death mechanism that could be associated with TNF-α and DHFR inhibition as among possible protein targets.

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Section: Lipinski's Rule and Admet Of Eurycomanone And Eurycomalactonementioning

confidence: 94%

Section: Molecular Docking Analysismentioning

confidence: 99%

Section: Lipinski's Rule and Admet Of Eurycomanone And Eurycomalactonementioning

confidence: 99%

Section: Lipinski's Rule and Admet Of Eurycomanone And Eurycomalactonementioning

confidence: 99%

Section: Lipinski's Rule and Admet Of Eurycomanone And Eurycomalactonementioning

confidence: 99%

See 3 more Smart Citations

In Vitro and In Silico Analysis of the Anti-cancer Effects of Eurycomanone and Eurycomalactone from <em>Eurycoma longifolia.</em>

Yunos¹,

Wahab²,

Al-Thiabat³

et al. 2023

Preprint

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Tumor Homing Chimeric Peptide Rhomboids to Improve Photodynamic Performance by Inhibiting Therapy‐Upregulated Cyclooxygenase‐2

Zhang,

Yu,

Chen

et al. 2024

Small

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Negative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as NP‐Mel) are fabricated to improve photodynamic performance by inhibiting PDT‐upregulated cyclooxygenase‐2 (COX‐2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic‐K(PpIX)CGNKRTR), which can encapsulate the COX‐2 inhibitor of meloxicam. The well dispersed NP‐Mel not only improves the drug stability and reactive oxygen species (ROS) production ability, but also increase the breast cancer targeted drug delivery to intensify the PDT effect. In vitro and in vivo studies verify that NP‐Mel will decrease the secretion of prostaglandin E2 (PGE2) after PDT treatment, inducing the downregulation of IL‐6 and TNF‐α expressions to suppress PDT induced inflammation. Ultimately, an improved PDT performance of NP‐Mel is achieved without inducing obvious systemic toxicity, which might inspire the development of sophisticated nanomedicine in consideration of the feedback induced therapeutic resistance.

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Preclinical evaluation of 68 Ga-labeled peptide CK2 for PET imaging of NRP-1 expression in vivo

Liu,

Cai,

et al. 2024

Eur J Nucl Med Mol Imaging

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tLyp–1: A peptide suitable to target NRP–1 receptor

Cited by 8 publications

References 64 publications

In Vitro and In Silico Analysis of the Anti-cancer Effects of Eurycomanone and Eurycomalactone from <em>Eurycoma longifolia.</em>

In Vitro and In Silico Analysis of the Anti-cancer Effects of Eurycomanone and Eurycomalactone from <em>Eurycoma longifolia.</em>

Tumor Homing Chimeric Peptide Rhomboids to Improve Photodynamic Performance by Inhibiting Therapy‐Upregulated Cyclooxygenase‐2

Preclinical evaluation of 68 Ga-labeled peptide CK2 for PET imaging of NRP-1 expression in vivo

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