6,6′-Dihydroxythiobinupharidine (DTBN) Purified from <i>Nuphar lutea</i> 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
Affiliations
Kamran Waidha
Defence Institute of High Altitude Research (DIHAR), Defence Research and Development Organisation (DRDO) Leh, Ladakh UT-194101, India
Nikhil Ponnoor Anto
The Shraga Segal Department of Microbiology, Immunology and Genetics Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 8400501, Israel
Divya Ram Jayaram
The Shraga Segal Department of Microbiology, Immunology and Genetics Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 8400501, Israel
Avi Golan-Goldhirsh
The Jacob Blaustein Institutes for Desert Research (BIDR), Sede Boqer Campus, French Associates Institute for Agriculture and Biotechnology of Drylands, Ben-Gurion University of the Negev, Beer Sheva 8499000, Israel
Saravanakumar Rajendran
Chemistry Division, Vellore Institute of Technology Chennai Campus, School of Advanced Sciences, Chennai 600127, India
Etta Livneh
The Shraga Segal Department of Microbiology, Immunology and Genetics Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 8400501, Israel
Jacob Gopas
The Shraga Segal Department of Microbiology, Immunology and Genetics Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 8400501, Israel
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.
