10-Alkoxy-anthracenyl-isoxazole analogs have sub-micromolar activity against a Glioblastoma multiforme cell line

Nathan S. Duncan; Michael J. Campbell; Donald S. Backos; Chun Li; Kevin C. Rider; Sascha Stump; Matthew J. Weaver; Mariusz P. Gajewski; Howard D. Beall; Philip Reigan; Nicholas R. Natale

doi:10.1016/j.bmc.2022.116911

10-Alkoxy-anthracenyl-isoxazole analogs have sub-micromolar activity against a Glioblastoma multiforme cell line

Nathan S. Duncan, Michael J. Campbell, Donald S. Backos, Chun Li, Kevin C. Rider, Sascha Stump, Matthew J. Weaver, Mariusz P. Gajewski, Howard D. Beall, Philip Reigan, Nicholas R. Natale

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3 Scopus citations

Abstract

A series of 10-alkoxy-Anthryl-isoxazole-pyrrole-doubletails (RO-AIMs) were synthesized using a crown ether assisted nucleophilic aromatic substitution followed by a modified Schotten-Baumann reaction. The novel RO-AIMs described here exhibit robust growth inhibition for the human SNB19 CNS glioblastoma cell line, and biphenyl analog 8c had activity in the nanomolar regime, which represents the most efficacious compound in the AIM series to date. Computational modeling for RO-AIMs binding in a ternary complex with c-myc quadruplex DNA and its helicase DHX36 is presented which represents our current working hypothesis.

Original language	English
Article number	116911
Journal	Bioorganic and Medicinal Chemistry
Volume	69
DOIs	https://doi.org/10.1016/j.bmc.2022.116911
State	Published - Sep 1 2022

Keywords

Anti-tumor
Isoxazole
Pyrrole
Quadruplex DNA
Synthesis

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Duncan, N. S., Campbell, M. J., Backos, D. S., Li, C., Rider, K. C., Stump, S., Weaver, M. J., Gajewski, M. P., Beall, H. D., Reigan, P., & Natale, N. R. (2022). 10-Alkoxy-anthracenyl-isoxazole analogs have sub-micromolar activity against a Glioblastoma multiforme cell line. Bioorganic and Medicinal Chemistry, 69, Article 116911. https://doi.org/10.1016/j.bmc.2022.116911

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title = "10-Alkoxy-anthracenyl-isoxazole analogs have sub-micromolar activity against a Glioblastoma multiforme cell line",

abstract = "A series of 10-alkoxy-Anthryl-isoxazole-pyrrole-doubletails (RO-AIMs) were synthesized using a crown ether assisted nucleophilic aromatic substitution followed by a modified Schotten-Baumann reaction. The novel RO-AIMs described here exhibit robust growth inhibition for the human SNB19 CNS glioblastoma cell line, and biphenyl analog 8c had activity in the nanomolar regime, which represents the most efficacious compound in the AIM series to date. Computational modeling for RO-AIMs binding in a ternary complex with c-myc quadruplex DNA and its helicase DHX36 is presented which represents our current working hypothesis.",

keywords = "Anti-tumor, Isoxazole, Pyrrole, Quadruplex DNA, Synthesis",

author = "Duncan, {Nathan S.} and Campbell, {Michael J.} and Backos, {Donald S.} and Chun Li and Rider, {Kevin C.} and Sascha Stump and Weaver, {Matthew J.} and Gajewski, {Mariusz P.} and Beall, {Howard D.} and Philip Reigan and Natale, {Nicholas R.}",

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doi = "10.1016/j.bmc.2022.116911",

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T1 - 10-Alkoxy-anthracenyl-isoxazole analogs have sub-micromolar activity against a Glioblastoma multiforme cell line

AU - Duncan, Nathan S.

AU - Campbell, Michael J.

AU - Backos, Donald S.

AU - Li, Chun

AU - Rider, Kevin C.

AU - Stump, Sascha

AU - Weaver, Matthew J.

AU - Gajewski, Mariusz P.

AU - Beall, Howard D.

AU - Reigan, Philip

AU - Natale, Nicholas R.

PY - 2022/9/1

Y1 - 2022/9/1

N2 - A series of 10-alkoxy-Anthryl-isoxazole-pyrrole-doubletails (RO-AIMs) were synthesized using a crown ether assisted nucleophilic aromatic substitution followed by a modified Schotten-Baumann reaction. The novel RO-AIMs described here exhibit robust growth inhibition for the human SNB19 CNS glioblastoma cell line, and biphenyl analog 8c had activity in the nanomolar regime, which represents the most efficacious compound in the AIM series to date. Computational modeling for RO-AIMs binding in a ternary complex with c-myc quadruplex DNA and its helicase DHX36 is presented which represents our current working hypothesis.

AB - A series of 10-alkoxy-Anthryl-isoxazole-pyrrole-doubletails (RO-AIMs) were synthesized using a crown ether assisted nucleophilic aromatic substitution followed by a modified Schotten-Baumann reaction. The novel RO-AIMs described here exhibit robust growth inhibition for the human SNB19 CNS glioblastoma cell line, and biphenyl analog 8c had activity in the nanomolar regime, which represents the most efficacious compound in the AIM series to date. Computational modeling for RO-AIMs binding in a ternary complex with c-myc quadruplex DNA and its helicase DHX36 is presented which represents our current working hypothesis.

KW - Anti-tumor

KW - Isoxazole

KW - Pyrrole

KW - Quadruplex DNA

KW - Synthesis

UR - http://www.scopus.com/inward/record.url?scp=85133238331&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2022.116911

DO - 10.1016/j.bmc.2022.116911

M3 - Article

C2 - 35792402

AN - SCOPUS:85133238331

SN - 0968-0896

VL - 69

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

M1 - 116911

ER -

10-Alkoxy-anthracenyl-isoxazole analogs have sub-micromolar activity against a Glioblastoma multiforme cell line

Abstract

Keywords

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