PMID- 31753699
OWN - NLM
STAT- MEDLINE
DCOM- 20210122
LR  - 20210122
IS  - 1464-3405 (Electronic)
IS  - 0960-894X (Linking)
VI  - 30
IP  - 2
DP  - 2020 Jan 15
TI  - Formation of 5alpha-dihydrotestosterone from 5alpha-androstane-3alpha,17beta-diol in prostate 
      cancer LAPC-4 cells - Identifying inhibitors of non-classical pathways producing 
      the most potent androgen.
PG  - 126783
LID - S0960-894X(19)30748-6 [pii]
LID - 10.1016/j.bmcl.2019.126783 [doi]
AB  - 5alpha-Dihydrotestosterone (5alpha-DHT) possesses a great affinity for the androgen 
      receptor (AR), and its binding to AR promotes the proliferation of prostate 
      cancer (PC) cells in androgen-dependent PC. Primarily synthesized from 
      testosterone (T) in testis, 5alpha-DHT could also be produced from 
      5alpha-androstane-3alpha,17beta-diol (3alpha-diol), an almost inactive androgen, following 
      non-classical pathways. We reported the chemical synthesis of non-commercially 
      available [4-(14)C]-3alpha-diol from [4-(14)C]-T, and the development of a biological 
      assay to identify inhibitors of the 5alpha-DHT formation from radiolabeled 3alpha-diol in 
      LAPC-4 cell PC model. We measured the inhibitory potency of 5alpha-androstane 
      derivatives against the formation of 5alpha-DHT, and inhibition curves were obtained 
      for the most potent compounds (IC(50) = 1.2-14.1 muM). The most potent inhibitor 
      25 (IC(50) = 1.2 muM) possesses a 4-(4-CF(3)-3-CH(3)O-benzyl)piperazinyl methyl 
      side chain at C3beta and 17beta-OH/17alpha-CCH functionalities at C17 of a 5alpha-androstane 
      core.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Boutin, Sophie
AU  - Boutin S
AD  - Laboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de 
      Quebec - Research Center, Quebec, QC, Canada; Department of Molecular Medicine, 
      Faculty of Medicine, Universite Laval, Quebec, QC, Canada.
FAU - Roy, Jenny
AU  - Roy J
AD  - Laboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de 
      Quebec - Research Center, Quebec, QC, Canada.
FAU - Maltais, Rene
AU  - Maltais R
AD  - Laboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de 
      Quebec - Research Center, Quebec, QC, Canada.
FAU - Poirier, Donald
AU  - Poirier D
AD  - Laboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de 
      Quebec - Research Center, Quebec, QC, Canada; Department of Molecular Medicine, 
      Faculty of Medicine, Universite Laval, Quebec, QC, Canada. Electronic address: 
      Donald.poirier@crchul.ulaval.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191109
PL  - England
TA  - Bioorg Med Chem Lett
JT  - Bioorganic & medicinal chemistry letters
JID - 9107377
RN  - 0 (Androgens)
RN  - 0 (Receptors, Androgen)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 25126-76-5 (Androstane-3,17-diol)
SB  - IM
MH  - Androgens/*metabolism
MH  - Androstane-3,17-diol/chemistry/*metabolism
MH  - Cell Line, Tumor
MH  - Dihydrotestosterone/chemistry/*metabolism
MH  - Humans
MH  - Male
MH  - Prostatic Neoplasms/metabolism/pathology
MH  - Receptors, Androgen/chemistry/metabolism
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - Androgen
OT  - Androstane derivative
OT  - LAPC-4 cells
OT  - Prostate cancer
OT  - Steroid
EDAT- 2019/11/23 06:00
MHDA- 2021/01/23 06:00
CRDT- 2019/11/23 06:00
PHST- 2019/09/11 00:00 [received]
PHST- 2019/10/21 00:00 [revised]
PHST- 2019/10/24 00:00 [accepted]
PHST- 2019/11/23 06:00 [pubmed]
PHST- 2021/01/23 06:00 [medline]
PHST- 2019/11/23 06:00 [entrez]
AID - S0960-894X(19)30748-6 [pii]
AID - 10.1016/j.bmcl.2019.126783 [doi]
PST - ppublish
SO  - Bioorg Med Chem Lett. 2020 Jan 15;30(2):126783. doi: 10.1016/j.bmcl.2019.126783. 
      Epub 2019 Nov 9.