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Carbonate and carbamate derivatives of 4-demethylpenclomedine as novel anticancer agents.

Morgan LR, Struck RF, Waud WR, LeBlanc B, Rodgers AH, Jursic BS - Cancer Chemother. Pharmacol. (2009)

Bottom Line: The purpose of this investigation was to synthesize a series of carbonate and carbamate derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma non-toxic metabolite of penclomedine (PEN) seen in patients.The major goal was to identify derivatives that are active in brain tumors.Carbonate and carbamate derivatives were found to be superior to DM-PEN against IC growing human glioblastoma xenografts.

View Article: PubMed Central - PubMed

Affiliation: DEKK-TEC Inc, New Orleans, LA, USA. lrm1579@aol.com

ABSTRACT

Purpose: The purpose of this investigation was to synthesize a series of carbonate and carbamate derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma non-toxic metabolite of penclomedine (PEN) seen in patients. DM-PEN has been observed to be an active antitumor agent in mouse human xenograft tumor models and non-neurotoxic in a rat model, however, activity in intracranially implanted human glioma xenograft models have not been reported. The major goal was to identify derivatives that are active in brain tumors.

Methods: Derivatives were prepared from DM-PEN and evaluated in vivo against human U251 glioblastoma, D54 glioblastoma and MX-1 breast tumor xenografts and mammary tumor 16/C that were implanted in the mammary fat pad or intracranially (IC).

Results: Carbonate and carbamate derivatives were found to be superior to DM-PEN against IC growing human glioblastoma xenografts.

Conclusion: The activity of the carbonates and carbamates against human tumor xenografts in vivo suggests consideration of these two series of derivatives of DM-PEN for clinical development.

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Related in: MedlinePlus

Carbamate analogs synthesized (MS values)
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Fig3: Carbamate analogs synthesized (MS values)

Mentions: Figures 2 and 3 show the structures, MS and yields of the carbonate and carbamate derivatives of DM-PEN prepared as described in “Materials and methods”. The vehicle for all the derivatives was as described in the “Materials and methods”, and tolerated well, however, in the human studies a soybean oil/egg yolk lecithin based-vehicle will be used to deliver the derivatives as an emulsion.Fig. 2


Carbonate and carbamate derivatives of 4-demethylpenclomedine as novel anticancer agents.

Morgan LR, Struck RF, Waud WR, LeBlanc B, Rodgers AH, Jursic BS - Cancer Chemother. Pharmacol. (2009)

Carbamate analogs synthesized (MS values)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2717391&req=5

Fig3: Carbamate analogs synthesized (MS values)
Mentions: Figures 2 and 3 show the structures, MS and yields of the carbonate and carbamate derivatives of DM-PEN prepared as described in “Materials and methods”. The vehicle for all the derivatives was as described in the “Materials and methods”, and tolerated well, however, in the human studies a soybean oil/egg yolk lecithin based-vehicle will be used to deliver the derivatives as an emulsion.Fig. 2

Bottom Line: The purpose of this investigation was to synthesize a series of carbonate and carbamate derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma non-toxic metabolite of penclomedine (PEN) seen in patients.The major goal was to identify derivatives that are active in brain tumors.Carbonate and carbamate derivatives were found to be superior to DM-PEN against IC growing human glioblastoma xenografts.

View Article: PubMed Central - PubMed

Affiliation: DEKK-TEC Inc, New Orleans, LA, USA. lrm1579@aol.com

ABSTRACT

Purpose: The purpose of this investigation was to synthesize a series of carbonate and carbamate derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma non-toxic metabolite of penclomedine (PEN) seen in patients. DM-PEN has been observed to be an active antitumor agent in mouse human xenograft tumor models and non-neurotoxic in a rat model, however, activity in intracranially implanted human glioma xenograft models have not been reported. The major goal was to identify derivatives that are active in brain tumors.

Methods: Derivatives were prepared from DM-PEN and evaluated in vivo against human U251 glioblastoma, D54 glioblastoma and MX-1 breast tumor xenografts and mammary tumor 16/C that were implanted in the mammary fat pad or intracranially (IC).

Results: Carbonate and carbamate derivatives were found to be superior to DM-PEN against IC growing human glioblastoma xenografts.

Conclusion: The activity of the carbonates and carbamates against human tumor xenografts in vivo suggests consideration of these two series of derivatives of DM-PEN for clinical development.

Show MeSH
Related in: MedlinePlus