PMID- 11488524
OWN - NLM
STAT- MEDLINE
DCOM- 20010830
LR  - 20190901
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 48
IP  - 1
DP  - 2001 Jul
TI  - Acyl derivatives of demethylpenclomedine, an antitumor-active, non-neurotoxic 
      metabolites of penclomedine.
PG  - 47-52
AB  - PURPOSE: The purpose of this investigation was to compare the antitumor 
      activities of a series of acyl derivatives of 4-demethylpenclomedine (DM-PEN), 
      the major plasma metabolite of penclomedine (PEN) observed to be an active 
      antitumor agent in vivo and non-neurotoxic in a rat model with that of DM-PEN. 
      METHODS: Acyl derivatives were prepared from DM-PEN and evaluated in vivo against 
      human MX-1 breast tumor xenografts implanted subcutaneously (s.c.) or 
      intracerebrally (i.c.). Several derivatives were also evaluated against other 
      human tumor xenografts and murine P388 leukemia cell lines. RESULTS: Several of 
      the acyl derivatives were found to be superior to DM-PEN against MX-1, human 
      ZR-75-1 breast tumor, human U251 CNS tumor and the P388 leukemia parent cell line 
      and lines resistant to cyclophosphamide and carmustine. 
      4-Demethyl-4-methoxyacetylpenclomedine showed inferior activity to current 
      clinical brain tumor drugs against a glioma cell line, superior activity to 
      temozolomide and procarbazine against the derived mismatch repair-deficient cell 
      line, and superior activity to cyclophosphamide and carmustine but inferior 
      activity to temozolomide against two ependymoma cell lines, all of which were 
      implanted s.c. CONCLUSION: Proposed mechanisms of activation and action of DM-PEN 
      and the acyl derivatives support the potential clinical superiority of the acyl 
      derivatives.
FAU - Struck, R F
AU  - Struck RF
AD  - Southern Research Institute, Birmingham, AL 35255-5305, USA. struck@sri.org
FAU - Tiwari, A
AU  - Tiwari A
FAU - Friedman, H S
AU  - Friedman HS
FAU - Keir, S
AU  - Keir S
FAU - Morgan, L R
AU  - Morgan LR
FAU - Waud, W R
AU  - Waud WR
LA  - eng
GR  - P01 CA34200/CA/NCI NIH HHS/United States
GR  - R44 CA85021/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Picolines)
RN  - 66Q80IL7CW (penclomedine)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology/toxicity
MH  - Brain Neoplasms/drug therapy
MH  - Humans
MH  - Mice
MH  - Neoplasm Transplantation
MH  - Picolines/metabolism/*pharmacology
MH  - Structure-Activity Relationship
MH  - Transplantation, Heterologous
EDAT- 2001/08/08 10:00
MHDA- 2001/08/31 10:01
CRDT- 2001/08/08 10:00
PHST- 2001/08/08 10:00 [pubmed]
PHST- 2001/08/31 10:01 [medline]
PHST- 2001/08/08 10:00 [entrez]
AID - 10.1007/s002800000255 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2001 Jul;48(1):47-52. doi: 10.1007/s002800000255.