Open Access
Pharmaceuticals, volume 16, issue 5, pages 735
Design, Synthesis, and Evaluation of Niclosamide Analogs as Therapeutic Agents for Enzalutamide-Resistant Prostate Cancer
Borui Kang
1, 2
,
Madhusoodanan Mottamal
1, 2
,
Qiu Zhong
1, 2
,
Melyssa Bratton
2
,
Changde Zhang
1, 2
,
Shanchun Guo
1, 2
,
Hossain Ahamed
2
,
Peng Ma
2
,
Qiang Zhang
1, 2
,
Guangdi Wang
1, 2
,
Florastina Payton-Stewart
1, 2
1
Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA
|
2
RCMI Cancer Research Center, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA
|
Publication type: Journal Article
Publication date: 2023-05-12
Journal:
Pharmaceuticals
Quartile SCImago
Q1
Quartile WOS
Q2
Impact factor: 4.6
ISSN: 14248247, 14248247
Drug Discovery
Pharmaceutical Science
Molecular Medicine
Abstract
Niclosamide effectively downregulates androgen receptor variants (AR-Vs) for treating enzalutamide and abiraterone-resistant prostate cancer. However, the poor pharmaceutical properties of niclosamide due to its solubility and metabolic instability have limited its clinical utility as a systemic treatment for cancer. A novel series of niclosamide analogs was prepared to systematically explore the structure–activity relationship and identify active AR-Vs inhibitors with improved pharmaceutical properties based on the backbone chemical structure of niclosamide. Compounds were characterized using 1H NMR, 13C NMR, MS, and elemental analysis. The synthesized compounds were evaluated for antiproliferative activity and downregulation of AR and AR-V7 in two enzalutamide-resistant cell lines, LNCaP95 and 22RV1. Several of the niclosamide analogs exhibited equivalent or improved anti-proliferation effects in LNCaP95 and 22RV1 cell lines (B9, IC50 LNCaP95 and 22RV1 = 0.130 and 0.0997 μM, respectively), potent AR-V7 down-regulating activity, and improved metabolic stability. In addition, both a traditional structure–activity relationship (SAR) and 3D-QSAR analysis were performed to guide further structural optimization. The presence of two -CF3 groups of the most active B9 in the sterically favorable field and the presence of the -CN group of the least active B7 in the sterically unfavorable field seem to make B9 more potent than B7 in the antiproliferative activity.
Top-30
Citations by journals
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1
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Cells
1 publication, 50%
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Russian Chemical Reviews
1 publication, 50%
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1
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Citations by publishers
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1
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Multidisciplinary Digital Publishing Institute (MDPI)
1 publication, 50%
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Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii
1 publication, 50%
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1
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- We do not take into account publications without a DOI.
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- Statistics recalculated weekly.
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Kang B. et al. Design, Synthesis, and Evaluation of Niclosamide Analogs as Therapeutic Agents for Enzalutamide-Resistant Prostate Cancer // Pharmaceuticals. 2023. Vol. 16. No. 5. p. 735.
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Kang B., Mottamal M., Zhong Q., Bratton M., Zhang C., Guo S., Ahamed H., Ma P., Zhang Q., Wang G., Payton-Stewart F. Design, Synthesis, and Evaluation of Niclosamide Analogs as Therapeutic Agents for Enzalutamide-Resistant Prostate Cancer // Pharmaceuticals. 2023. Vol. 16. No. 5. p. 735.
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TY - JOUR
DO - 10.3390/ph16050735
UR - https://doi.org/10.3390/ph16050735
TI - Design, Synthesis, and Evaluation of Niclosamide Analogs as Therapeutic Agents for Enzalutamide-Resistant Prostate Cancer
T2 - Pharmaceuticals
AU - Kang, Borui
AU - Mottamal, Madhusoodanan
AU - Zhong, Qiu
AU - Bratton, Melyssa
AU - Zhang, Changde
AU - Guo, Shanchun
AU - Ahamed, Hossain
AU - Ma, Peng
AU - Zhang, Qiang
AU - Wang, Guangdi
AU - Payton-Stewart, Florastina
PY - 2023
DA - 2023/05/12 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 735
IS - 5
VL - 16
SN - 1424-8247
SN - 1424-8247
ER -
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@article{2023_Kang,
author = {Borui Kang and Madhusoodanan Mottamal and Qiu Zhong and Melyssa Bratton and Changde Zhang and Shanchun Guo and Hossain Ahamed and Peng Ma and Qiang Zhang and Guangdi Wang and Florastina Payton-Stewart},
title = {Design, Synthesis, and Evaluation of Niclosamide Analogs as Therapeutic Agents for Enzalutamide-Resistant Prostate Cancer},
journal = {Pharmaceuticals},
year = {2023},
volume = {16},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {may},
url = {https://doi.org/10.3390/ph16050735},
number = {5},
pages = {735},
doi = {10.3390/ph16050735}
}
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Kang, Borui, et al. “Design, Synthesis, and Evaluation of Niclosamide Analogs as Therapeutic Agents for Enzalutamide-Resistant Prostate Cancer.” Pharmaceuticals, vol. 16, no. 5, May. 2023, p. 735. https://doi.org/10.3390/ph16050735.