Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer

Alireza Basiri; Wenting Zhang; Jered Garrison

doi:10.1016/j.bmcl.2020.127697

Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer

Alireza Basiri, Wenting Zhang, Jered Garrison

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

1 Scopus citations

Abstract

Tumor hypoxia has been widely explored over the years as a diagnostic and therapeutic marker. Herein, we have reported the design and synthesis of a series of dinitrobenzamide mustards (DNBM) based on the PR-104A hypoxia-selective prodrug. Specifically, we explored the impact of various leaving groups and the introduction of a carboxylic acid group on the biological performance of the DNBM constructs. Once in hand, the Log D values, cytotoxicity in PC-3 and DU-145 human prostate cancer cells lines and the hypoxia selectivities of the DNBM analogs were examined. Overall, the DNBM constructs were found to be tolerant to modifications with none of the explored modifications substantially degrading the cytotoxic potential of the constructs.

Original language	English (US)
Article number	127697
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	31
DOIs	https://doi.org/10.1016/j.bmcl.2020.127697
State	Published - Jan 1 2021

Keywords

DNBM
Hypoxia
Prodrug
Prostate cancer

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2020.127697

Cite this

@article{1eeeaa206bd94ce191c920fe74dc6178,

title = "Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer",

abstract = "Tumor hypoxia has been widely explored over the years as a diagnostic and therapeutic marker. Herein, we have reported the design and synthesis of a series of dinitrobenzamide mustards (DNBM) based on the PR-104A hypoxia-selective prodrug. Specifically, we explored the impact of various leaving groups and the introduction of a carboxylic acid group on the biological performance of the DNBM constructs. Once in hand, the Log D values, cytotoxicity in PC-3 and DU-145 human prostate cancer cells lines and the hypoxia selectivities of the DNBM analogs were examined. Overall, the DNBM constructs were found to be tolerant to modifications with none of the explored modifications substantially degrading the cytotoxic potential of the constructs.",

keywords = "DNBM, Hypoxia, Prodrug, Prostate cancer",

author = "Alireza Basiri and Wenting Zhang and Jered Garrison",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

year = "2021",

month = jan,

day = "1",

doi = "10.1016/j.bmcl.2020.127697",

language = "English (US)",

volume = "31",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

}

TY - JOUR

T1 - Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer

AU - Basiri, Alireza

AU - Zhang, Wenting

AU - Garrison, Jered

PY - 2021/1/1

Y1 - 2021/1/1

N2 - Tumor hypoxia has been widely explored over the years as a diagnostic and therapeutic marker. Herein, we have reported the design and synthesis of a series of dinitrobenzamide mustards (DNBM) based on the PR-104A hypoxia-selective prodrug. Specifically, we explored the impact of various leaving groups and the introduction of a carboxylic acid group on the biological performance of the DNBM constructs. Once in hand, the Log D values, cytotoxicity in PC-3 and DU-145 human prostate cancer cells lines and the hypoxia selectivities of the DNBM analogs were examined. Overall, the DNBM constructs were found to be tolerant to modifications with none of the explored modifications substantially degrading the cytotoxic potential of the constructs.

AB - Tumor hypoxia has been widely explored over the years as a diagnostic and therapeutic marker. Herein, we have reported the design and synthesis of a series of dinitrobenzamide mustards (DNBM) based on the PR-104A hypoxia-selective prodrug. Specifically, we explored the impact of various leaving groups and the introduction of a carboxylic acid group on the biological performance of the DNBM constructs. Once in hand, the Log D values, cytotoxicity in PC-3 and DU-145 human prostate cancer cells lines and the hypoxia selectivities of the DNBM analogs were examined. Overall, the DNBM constructs were found to be tolerant to modifications with none of the explored modifications substantially degrading the cytotoxic potential of the constructs.

KW - DNBM

KW - Hypoxia

KW - Prodrug

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=85096869785&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85096869785&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2020.127697

DO - 10.1016/j.bmcl.2020.127697

M3 - Article

C2 - 33220402

AN - SCOPUS:85096869785

SN - 0960-894X

VL - 31

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

M1 - 127697

ER -

Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this