One-pot two-step catalytic synthesis of 6-amino-2-pyridone-3,5-dicarbonitriles enabling anti-cancer bioactivity

Lynden G. Nicely; Ruturajsinh M. Vala; Dipti B. Upadhyay; Joaquina Nogales; Celestine  Chi; Sourav Banerjee; Hitendra M. Patel

doi:10.1039/D2RA03579K

One-pot two-step catalytic synthesis of 6-amino-2-pyridone-3,5-dicarbonitriles enabling anti-cancer bioactivity

Lynden G. Nicely, Ruturajsinh M. Vala, Dipti B. Upadhyay, Joaquina Nogales, Celestine Chi, Sourav Banerjee (Lead / Corresponding author), Hitendra M. Patel (Lead / Corresponding author)

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Abstract

We report a one-pot two-step synthesis of a bioactive 6-amino-2-pyridone-3,5-dicarbonitrile derivative using natural product catalysts betaine and guanidine carbonate. Anti-cancer bioactivity was observed in specific molecules within the library of 16 derivatives. Out of the compounds, 5o had the most potent anti-cancer activity against glioblastoma cells and was selected for further study. Compound 5o showed anti-cancer properties against liver, breast, lung cancers as well as primary patient-derived glioblastoma cell lines. Furthermore, 5o in combination with specific clinically relevant small molecule inhibitors induced enhanced cytotoxicity in glioblastoma cells. Through our current work, we establish a promising 6-amino-2-pyridone-3,5-dicarbonitrile based lead compound with anti-cancer activity either on its own or in combination with specific clinically relevant small molecule kinase and proteasome inhibitors.

Original language	English
Pages (from-to)	23889-23897
Number of pages	9
Journal	RSC Advances
Volume	12
Issue number	37
Early online date	24 Aug 2022
DOIs	https://doi.org/10.1039/D2RA03579K
Publication status	Published - 24 Aug 2022

Keywords

6-amino-2-pyridone-3
5-dicarbonitriles
betaine
guanidine carbonate
one-pot two-step reaction
cancer

ASJC Scopus subject areas

General Chemical Engineering
General Chemistry

UN SDGs

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

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10.1039/D2RA03579KLicence: CC BY

Final published versionFinal published version, 1.03 MBLicence: CC BY

Cite this

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title = "One-pot two-step catalytic synthesis of 6-amino-2-pyridone-3,5-dicarbonitriles enabling anti-cancer bioactivity",

abstract = "We report a one-pot two-step synthesis of a bioactive 6-amino-2-pyridone-3,5-dicarbonitrile derivative using natural product catalysts betaine and guanidine carbonate. Anti-cancer bioactivity was observed in specific molecules within the library of 16 derivatives. Out of the compounds, 5o had the most potent anti-cancer activity against glioblastoma cells and was selected for further study. Compound 5o showed anti-cancer properties against liver, breast, lung cancers as well as primary patient-derived glioblastoma cell lines. Furthermore, 5o in combination with specific clinically relevant small molecule inhibitors induced enhanced cytotoxicity in glioblastoma cells. Through our current work, we establish a promising 6-amino-2-pyridone-3,5-dicarbonitrile based lead compound with anti-cancer activity either on its own or in combination with specific clinically relevant small molecule kinase and proteasome inhibitors.",

keywords = "6-amino-2-pyridone-3, 5-dicarbonitriles, betaine, guanidine carbonate, one-pot two-step reaction, cancer",

author = "Nicely, {Lynden G.} and Vala, {Ruturajsinh M.} and Upadhyay, {Dipti B.} and Joaquina Nogales and Celestine Chi and Sourav Banerjee and Patel, {Hitendra M.}",

note = "Funding Information: SB is funded by the Cancer Research UK EDDPMA-May21\100005, Tenovus Scotland T21-05, and Royal Society RGS\R2\212056. The authors thank the Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar for valuable support. The authors are thankful to the Biomolecular NMR center Uppsala, which is funded by the Department of Chemistry-BMC and the Disciplinary Domain of Medicine and Pharmacy. The graphical abstract was generated in part using Biorender.",

year = "2022",

month = aug,

day = "24",

doi = "10.1039/D2RA03579K",

language = "English",

volume = "12",

pages = "23889--23897",

journal = "RSC Advances",

issn = "2046-2069",

publisher = "Royal Society of Chemistry",

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T1 - One-pot two-step catalytic synthesis of 6-amino-2-pyridone-3,5-dicarbonitriles enabling anti-cancer bioactivity

AU - Nicely, Lynden G.

AU - Vala, Ruturajsinh M.

AU - Upadhyay, Dipti B.

AU - Nogales, Joaquina

AU - Chi, Celestine

AU - Banerjee, Sourav

AU - Patel, Hitendra M.

N1 - Funding Information: SB is funded by the Cancer Research UK EDDPMA-May21\100005, Tenovus Scotland T21-05, and Royal Society RGS\R2\212056. The authors thank the Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar for valuable support. The authors are thankful to the Biomolecular NMR center Uppsala, which is funded by the Department of Chemistry-BMC and the Disciplinary Domain of Medicine and Pharmacy. The graphical abstract was generated in part using Biorender.

PY - 2022/8/24

Y1 - 2022/8/24

N2 - We report a one-pot two-step synthesis of a bioactive 6-amino-2-pyridone-3,5-dicarbonitrile derivative using natural product catalysts betaine and guanidine carbonate. Anti-cancer bioactivity was observed in specific molecules within the library of 16 derivatives. Out of the compounds, 5o had the most potent anti-cancer activity against glioblastoma cells and was selected for further study. Compound 5o showed anti-cancer properties against liver, breast, lung cancers as well as primary patient-derived glioblastoma cell lines. Furthermore, 5o in combination with specific clinically relevant small molecule inhibitors induced enhanced cytotoxicity in glioblastoma cells. Through our current work, we establish a promising 6-amino-2-pyridone-3,5-dicarbonitrile based lead compound with anti-cancer activity either on its own or in combination with specific clinically relevant small molecule kinase and proteasome inhibitors.

AB - We report a one-pot two-step synthesis of a bioactive 6-amino-2-pyridone-3,5-dicarbonitrile derivative using natural product catalysts betaine and guanidine carbonate. Anti-cancer bioactivity was observed in specific molecules within the library of 16 derivatives. Out of the compounds, 5o had the most potent anti-cancer activity against glioblastoma cells and was selected for further study. Compound 5o showed anti-cancer properties against liver, breast, lung cancers as well as primary patient-derived glioblastoma cell lines. Furthermore, 5o in combination with specific clinically relevant small molecule inhibitors induced enhanced cytotoxicity in glioblastoma cells. Through our current work, we establish a promising 6-amino-2-pyridone-3,5-dicarbonitrile based lead compound with anti-cancer activity either on its own or in combination with specific clinically relevant small molecule kinase and proteasome inhibitors.

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KW - 5-dicarbonitriles

KW - betaine

KW - guanidine carbonate

KW - one-pot two-step reaction

KW - cancer

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U2 - 10.1039/D2RA03579K

DO - 10.1039/D2RA03579K

M3 - Article

SN - 2046-2069

VL - 12

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EP - 23897

JO - RSC Advances

JF - RSC Advances

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ER -

One-pot two-step catalytic synthesis of 6-amino-2-pyridone-3,5-dicarbonitriles enabling anti-cancer bioactivity

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Establishing the Oncogenic Phosphoproteome of Glioblastoma

Secreted Phosphoproteme In Blood As Early Detection And Risk Stratification Biomarkers Of Glioma

Cite this

One-pot two-step catalytic synthesis of 6-amino-2-pyridone-3,5-dicarbonitriles enabling anti-cancer bioactivity

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

Establishing the Oncogenic Phosphoproteome of Glioblastoma

Secreted Phosphoproteme In Blood As Early Detection And Risk Stratification Biomarkers Of Glioma

Cite this