A virtual insight into bioactive compounds of ginger as potential inhibitors of nek7 for cancer management | [Advancements in life sciences • 2024]

Author(s):

1. Akram Ahmed Aloqbi: Department of Biological Science, Faculty of Science, University of Jeddah, Jeddah , Saudi Arabia

Abstract:

Background: NIMA-related kinase 7 (NEK7) is a serine/threonine kinase that is required for cell cycle progression, particularly mitotic spindle formation and cytokinesis, and has been linked to various cancers. Furthermore, NEK7 modulates the NLRP3 inflammasome, which activates Caspase-1 and causes cell pyroptosis. A growing body of studies indicates that ginger has the ability to prevent and treat a variety of health issues. Methods: In this study, 383 distinct bioactive compounds were extracted from the LOTUS database from Zingiber officinale and were screened against NEK7 protein using the PyRx 0.8 software. The top six hits' physicochemical characteristics, molecular descriptors, and natural product-likeness ratings were assessed using the LOTUS database. Results: The compounds LTS0101379, LTS0022317, TS0094590, LTS0231343, LTS0085481, and LTS0110340 showed high affinity for NEK7, forming interactions with critical amino acid residues. Notably, these compounds had multiple interactions with amino acid residues similar to those of the control compound Dabrafenib. Furthermore, the molecular properties and descriptors of these compounds indicated favorable drug-like properties. Conclusion: These findings highlight the potential of these compounds as NEK7 inhibitors for cancer management, though additional experimental validation is required.

Page(s): 856-861

DOI: DOI not available

Published: Journal: Advancements in life sciences, Volume: 11, Issue: 4, Year: 2024

Keywords:

Zingiber officinale , cancer , NEK7 , Virtual screening Druglikenes

References:

[1] .2015 .related kinase-7 in squamous cell carcinoma of the head and neck. Molecular Cancer Research, 13(2) : 293-304.

[2] Eisa NH,Jilani Y,Kainth K,Redd P,Lu S .2019 .The cochaperone UNC45A is essential for the expression of mitotic kinase NEK7 and tumorigenesis. Journal of Biological Chemistry, 294(14) : 5246-5260.

[3] Yan Z,Qu J,Li Z,Yi J,Su Y,Promotes Pancreatic Cancer Progression And Its Expression Is Correlated With Poor Prognosis Y .2021 .. , 11 : 705797.

[4] Zhou L,Wang Z,Xu X,Wan Y,Qu K .2016 .Nek7 is overexpressed in hepatocellular carcinoma and promotes hepatocellular carcinoma cell proliferation in vitro and in vivo. Oncotarget, 7(14) : 18620-18630.

[5] Capra M,Nuciforo PG,Confalonieri S,Quarto M,Bianchi M .2006 .Frequent alterations in the expression of serine/threonine kinases in human cancers. Cancer Research, 66(16) : 8147-8154.

[6] Edible .2016 .-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer. Biomaterials, 101 : 321-340.

[7] .2014 .Synthesis and quorum sensing inhibitory activity of key phenolic compounds of ginger and their derivatives. Food Chemistry, 159 : 451-457.

[8] Citronberg J,Bostick R,Ahearn T,Turgeon DK,Ruffin MT .2013 .Effects of ginger supplementation on cell-cycle biomarkers in the normal-appearing colonic mucosa of patients at increased risk for colorectal cancer: results from a pilot, randomized, and controlled trial. Cancer Prevention Research, 6(4) : 271-281.

[9] Ho SC,Chang KS,Lin CC .2013 .Anti-neuroinflammatory capacity of fresh ginger is attributed mainly to 10-gingerol. Food Chemistry, 141(3) : 3183-3191.

[10] Nutrition Molecular .2017 .. , 61(10) : 1700139.

[11] Wei CK,Tsai YH,Korinek M,Hung PH,El-Shazly M .2017 .- Paradol and 6-Shogaol, the Pungent Compounds of Ginger, Promote Glucose Utilization in Adipocytes and Myotubes, and 6-Paradol Reduces Blood Glucose in High-Fat Diet-Fed Mice. International Journal of Molecular Sciences, 18(1) : 168.

[12] .2013 .Ginger and its pungent constituents non-competitively inhibit activation of human recombinant and native 5-HT3 receptors of enteric neurons. Neurogastroenterology & Motility, 25(5) : 439-e302.

[13] .2013 .Effects of ginger and its constituents on airway smooth muscle relaxation and calcium regulation. American Journal of Respiratory Cell and Molecular Biology, 48(2) : 157-163.

[14] Rutz A,Sorokina M,Galgonek J,Mietchen D,Willighagen E .2022 .The LOTUS initiative for open knowledge management in natural products research. , 11 : e70780.

[15] Fry AM,O'Regan L,Sabir SR,Bayliss R .2012 .Cell cycle regulation by the NEK family of protein kinases. Journal of Cell Science, 125(19) : 4423-4433.

[16] Oakley BR,Morris NR .1983 .A mutation in Aspergillus nidulans that blocks the transition from interphase to prophase. The Journal of Cell Biology, 96(4) : 1155-1158.

[17] Genetics Research .1975 .. , 26(3) : 237-254.

[18] .2015 .Targeting cancer with kinase inhibitors. The Journal of Clinical Investigation, 125(5) : 1780-1789.

[19] Lapenna S,Giordano A .2009 .Cell cycle kinases as therapeutic targets for cancer. Nature Reviews Drug Discovery, 8(7) : 547-566.

[20] Moraes EC,Meirelles GV,Honorato RV,De Souza TD,De Souza EE .2015 .Kinase inhibitor profile for human nek1, nek6, and nek7 and analysis of the structural basis for inhibitor specificity. Molecules, 20(1) : 1176-1191.

[21] .2016 .Comparative inhibition study of compounds identified in the methanolic extract of Apamarga Kshara against Trichomonas vaginalis carbamate kinase (TvCK): an enzoinformatics approach. Interdisciplinary Sciences: Computational Life Sciences, 8 : 357-365.

[22] Advancements in Life Sciences .2024 .. , 11(1) : 237-245.

[23] .2019 .Structure-based virtual screening and molecular docking for the identification of potential novel EGFRkinase inhibitors against ovarian cancer. Bioinformation, 15(4) : 287.

[24] Sayed Murad HA,Rafeeq MM,Alqahtani SM,Rajab BS,Alghamdi S .2023 .Molecular docking analysis of AGTR1 antagonists. , 19(3) : 284-289.

[25] Kamal MA,Baeissa HM,Hakeem IJ,Alazragi RS,Hazzazi MS .2023 .Insights from the molecular docking analysis of EGFR antagonists. , 19(3) : 260-265.

[26] Mahomoodally MF,Aumeeruddy MZ,Rengasamy KR,Roshan S,Hammad S .2021 .Ginger and its active compounds in cancer therapy: From folk uses to nanotherapeutic applications. In Seminars in Cancer Biology, 69 : 140-149.

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