SYNTHESIS OF PHOSPHOCHOLINE AND QUATERNARY AMINE ETHER LIPIDS AND EVALUATION OF IN-VITRO ANTINEOPLASTIC ACTIVITY


MORRISNATSCHKE S., GUMUS F., MARASCO C., MEYER K., MARX M., PIANTADOSI C., ...Daha Fazla

JOURNAL OF MEDICINAL CHEMISTRY, cilt.36, ss.2018-2025, 1993 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 36 Konu: 14
  • Basım Tarihi: 1993
  • Doi Numarası: 10.1021/jm00066a011
  • Dergi Adı: JOURNAL OF MEDICINAL CHEMISTRY
  • Sayfa Sayıları: ss.2018-2025

Özet

The in vitro antineoplastic activity of many phosphorus-containing (e.g., phosphocholines) and non-phosphorus-containing (e.g., quaternary ammonium salts) ether lipids has been evaluated in the HL-60 promyelocytic cell line. These compounds are analogues of ET-18-OMe (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine). Structural modification of 1-(alkylamido)-,-(alkylthio)-, and -(alkyloxy)propyl backbones has provided further insight into the structure-activity relationships of these lipids. In this study, along saturated C-1 chain and a three-carbon backbone with a single short C-2 substituent were preferred. At the positively charged nitrogen of phosphocholines, fewer than three substituents caused a significant loss of activity, and substituents larger than methyl decreased activity slightly. In the nonphosphorus compounds, many nitrogen heterocycles and also a sulfonium moiety were incorporated without changing the degree of activity; however, a thiazolium group decreased activity. The most active compound, 29 [N-[3-(hexadecyloxy)-2-methoxypropyl]-3-(hydroxymethyl)pyridinium bromide], was approximately twice as active as the reference standard, ET-18-OMe, in a trypan blue dye exclusion assay.