Limits...
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.

Show MeSH

Related in: MedlinePlus

Where: PEN, R = CH3 and DM-PEN, R = H
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2717391&req=5

Fig1: Where: PEN, R = CH3 and DM-PEN, R = H

Mentions: Chemical characterizations of the derivatives are available upon request (LRM1579@aol.com). DM-CHOC-PEN has been selected for clinical trials; m.p., NMR (varian unity) and CHN elemental analyses are presented below and MS (Perkin Elmer Series 200) in Fig. 1: m.p. 171–172°C); anal. C35H48Cl5NO4: calc. C, 58.9, H, 6.7, N, 1.9; found: 58.7, H, 6.9, N, 1.8; 13C-NMR (400 MHz, varian unity, CDCl3) δ 155.568, 153.879, 149.261, 147.659, 138.614, 123.545, 117.544, 114.879, 95.622, 80.831, 56.673, 56.156, 55.472, 49.980, 42.341, 39.726, 39.544, 37.665, 36.769, 36.551, 36.216, 35.815, 31.933, 31.860, 28.255, 28.044, 27.469, 24.315, 23.878, 22.859, 22.611, 21.104, 19.312, 18.773, and 11.920 ppm; 1H-NMR(400 MHz, varian unity: σ 5.428 (1H, d, J = 6.4 Hz), 4.629 (1H, m), 4.113 (3H, s), 2.516 (2H, m), and between 0.6 and 2.1 ppm multiple signals for all other hydrogen.Fig. 1


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)

Where: PEN, R = CH3 and DM-PEN, R = H
© Copyright Policy
Related In: Results  -  Collection

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

Fig1: Where: PEN, R = CH3 and DM-PEN, R = H
Mentions: Chemical characterizations of the derivatives are available upon request (LRM1579@aol.com). DM-CHOC-PEN has been selected for clinical trials; m.p., NMR (varian unity) and CHN elemental analyses are presented below and MS (Perkin Elmer Series 200) in Fig. 1: m.p. 171–172°C); anal. C35H48Cl5NO4: calc. C, 58.9, H, 6.7, N, 1.9; found: 58.7, H, 6.9, N, 1.8; 13C-NMR (400 MHz, varian unity, CDCl3) δ 155.568, 153.879, 149.261, 147.659, 138.614, 123.545, 117.544, 114.879, 95.622, 80.831, 56.673, 56.156, 55.472, 49.980, 42.341, 39.726, 39.544, 37.665, 36.769, 36.551, 36.216, 35.815, 31.933, 31.860, 28.255, 28.044, 27.469, 24.315, 23.878, 22.859, 22.611, 21.104, 19.312, 18.773, and 11.920 ppm; 1H-NMR(400 MHz, varian unity: σ 5.428 (1H, d, J = 6.4 Hz), 4.629 (1H, m), 4.113 (3H, s), 2.516 (2H, m), and between 0.6 and 2.1 ppm multiple signals for all other hydrogen.Fig. 1

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