6,6′-dihydroxythiobinupharidine (Dtbn) purified from nuphar lutea leaves is an inhibitor of protein kinase c catalytic activity

Kamran Waidha; Nikhil Ponnoor Anto; Divya Ram Jayaram; Avi Golan-Goldhirsh; Saravanakumar Rajendran; Etta Livneh; Jacob Gopas

doi:10.3390/molecules26092785

6,6^′-dihydroxythiobinupharidine (Dtbn) purified from nuphar lutea leaves is an inhibitor of protein kinase c catalytic activity

Kamran Waidha, Nikhil Ponnoor Anto, Divya Ram Jayaram, Avi Golan-Goldhirsh, Saravanakumar Rajendran, Etta Livneh, Jacob Gopas

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Water lily (Nuphar) bioactive extracts have been widely used in traditional medicine owing to their multiple applications against human ailments. Phyto-active Nuphar extracts and their purified and synthetic derivatives have attracted the attention of ethnobotanists and biochemists. Here, we report that 6,6^′-dihydroxythiobinupharidine (DTBN), purified from extracts of Nuphar lutea (L.) Sm. leaves, is an effective inhibitor of the kinase activity of members of the protein kinase C (PKC) family using in vitro and in silico approaches. We demonstrate that members of the conventional subfamily of PKCs, PKCα and PKCγ, were more sensitive to DTBN inhibition as compared to novel or atypical PKCs. Molecular docking analysis demonstrated the interaction of DTBN, with the kinase domain of PKCs depicting the best affinity towards conventional PKCs, in accordance with our in vitro kinase activity data. The current study reveals novel targets for DTBN activity, functioning as an inhibitor for PKCs kinase activity. Thus, this and other data indicate that DTBN modulates key cellular signal transduction pathways relevant to disease biology, including cancer.

Original language	English
Article number	2785
Journal	Molecules
Volume	26
Issue number	9
DOIs	https://doi.org/10.3390/molecules26092785
State	Published - 1 Jan 2021

Keywords

6,6-dihydroxythiobinupharidine (DTBN)
Homology docking modeling
Kinase inhibitor
Nuphar lutea
Protein kinase C (PKC)
Ramachandran plot

ASJC Scopus subject areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/molecules26092785

Cite this

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title = "6,6′-dihydroxythiobinupharidine (Dtbn) purified from nuphar lutea leaves is an inhibitor of protein kinase c catalytic activity",

abstract = "Water lily (Nuphar) bioactive extracts have been widely used in traditional medicine owing to their multiple applications against human ailments. Phyto-active Nuphar extracts and their purified and synthetic derivatives have attracted the attention of ethnobotanists and biochemists. Here, we report that 6,6′-dihydroxythiobinupharidine (DTBN), purified from extracts of Nuphar lutea (L.) Sm. leaves, is an effective inhibitor of the kinase activity of members of the protein kinase C (PKC) family using in vitro and in silico approaches. We demonstrate that members of the conventional subfamily of PKCs, PKCα and PKCγ, were more sensitive to DTBN inhibition as compared to novel or atypical PKCs. Molecular docking analysis demonstrated the interaction of DTBN, with the kinase domain of PKCs depicting the best affinity towards conventional PKCs, in accordance with our in vitro kinase activity data. The current study reveals novel targets for DTBN activity, functioning as an inhibitor for PKCs kinase activity. Thus, this and other data indicate that DTBN modulates key cellular signal transduction pathways relevant to disease biology, including cancer.",

keywords = "6,6-dihydroxythiobinupharidine (DTBN), Homology docking modeling, Kinase inhibitor, Nuphar lutea, Protein kinase C (PKC), Ramachandran plot",

author = "Kamran Waidha and Anto, {Nikhil Ponnoor} and Jayaram, {Divya Ram} and Avi Golan-Goldhirsh and Saravanakumar Rajendran and Etta Livneh and Jacob Gopas",

note = "Funding Information: Funding: This research was supported by The Israel Science Foundation (grant No. 1864/16 [E.L., D.R.J. and N.P.A.]. Grant (No. 3-0-7374) from the Israel Ministry of Health [A.G.G. and J.G.]. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Waidha, Kamran

AU - Anto, Nikhil Ponnoor

AU - Jayaram, Divya Ram

AU - Golan-Goldhirsh, Avi

AU - Rajendran, Saravanakumar

AU - Livneh, Etta

AU - Gopas, Jacob

N1 - Funding Information: Funding: This research was supported by The Israel Science Foundation (grant No. 1864/16 [E.L., D.R.J. and N.P.A.]. Grant (No. 3-0-7374) from the Israel Ministry of Health [A.G.G. and J.G.]. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - Water lily (Nuphar) bioactive extracts have been widely used in traditional medicine owing to their multiple applications against human ailments. Phyto-active Nuphar extracts and their purified and synthetic derivatives have attracted the attention of ethnobotanists and biochemists. Here, we report that 6,6′-dihydroxythiobinupharidine (DTBN), purified from extracts of Nuphar lutea (L.) Sm. leaves, is an effective inhibitor of the kinase activity of members of the protein kinase C (PKC) family using in vitro and in silico approaches. We demonstrate that members of the conventional subfamily of PKCs, PKCα and PKCγ, were more sensitive to DTBN inhibition as compared to novel or atypical PKCs. Molecular docking analysis demonstrated the interaction of DTBN, with the kinase domain of PKCs depicting the best affinity towards conventional PKCs, in accordance with our in vitro kinase activity data. The current study reveals novel targets for DTBN activity, functioning as an inhibitor for PKCs kinase activity. Thus, this and other data indicate that DTBN modulates key cellular signal transduction pathways relevant to disease biology, including cancer.

AB - Water lily (Nuphar) bioactive extracts have been widely used in traditional medicine owing to their multiple applications against human ailments. Phyto-active Nuphar extracts and their purified and synthetic derivatives have attracted the attention of ethnobotanists and biochemists. Here, we report that 6,6′-dihydroxythiobinupharidine (DTBN), purified from extracts of Nuphar lutea (L.) Sm. leaves, is an effective inhibitor of the kinase activity of members of the protein kinase C (PKC) family using in vitro and in silico approaches. We demonstrate that members of the conventional subfamily of PKCs, PKCα and PKCγ, were more sensitive to DTBN inhibition as compared to novel or atypical PKCs. Molecular docking analysis demonstrated the interaction of DTBN, with the kinase domain of PKCs depicting the best affinity towards conventional PKCs, in accordance with our in vitro kinase activity data. The current study reveals novel targets for DTBN activity, functioning as an inhibitor for PKCs kinase activity. Thus, this and other data indicate that DTBN modulates key cellular signal transduction pathways relevant to disease biology, including cancer.

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