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Structure-cytotoxicity studies on alkyl lysophospholipids and some analogs in leukemic blasts of human origin in vitro

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Lipids

Abstract

Eleven lipids have been tested for cytotoxic (trypan blue dye exclusion) activity in cells from eight freshly explanted human leukemias in vitro. 4-Aminomethyl-1-[2,3-(di-N-decyloxy)N-propyl]-4-phenylpiperidine (CP-46,665), 1-mercapto-hexadecyl-2-methoxymethyl-rac-glycero-3-phosphocholine (BM 41.440), the 2-acetamide analog of platelet-activating factor (PAF) and 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) were found among the most active compounds. 2-Lysophosphatidylcholine (2-LPC) showed the lowest activity. However, in addition there was variation among the results regarding the activity of the 1-octadecyl-rac-glycero-3-phosphocholine (ET-18-OH) and its D- and L-forms, but a significantly higher cytotoxic activity of D-ET-18-OH compared with L-ET-18-OH on the basis of 2-LPC as control after an incubation time of 48 hr. We conclude that with the limited number of structures available, this type of study is not sufficient to yield further information about the mode of the accumulation and toxicity of this type of lipids.

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Abbreviations

ALP:

alkyl lysophospholipid derivative(s)

2-LPC:

2-lysophosphatidylcholine

ANLL:

acute non-lymphoblastic leukemia

ALL:

acute lymphoblastic leukemia

CML/BC:

chronic myeloid leukemia/blast crisis

PAF:

platelet-activating factor

CP-46,665:

4-aminomethyl-1-[2,3-(di-N-decyloxy)N-propyl]-4-phenyl-piperidine

BM 41.440:

rac-1-mercapto-hexadecyl-2-methoxymethyl-rac-glycero-3-phosphocholine

ET-18-OH:

1-O-octadecyl-rac-glycero-3-phosphocholine

ET-18-OCH3 :

1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine

ET-18-H:

1-O-octadecylpropane-3-phosphocholine

ET-12-H:

1-O-dodecylpropanediol-3-phosphocholine

References

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Danhauser, S., Berdel, W.E., Schick, H.D. et al. Structure-cytotoxicity studies on alkyl lysophospholipids and some analogs in leukemic blasts of human origin in vitro. Lipids 22, 911–915 (1987). https://doi.org/10.1007/BF02535553

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  • DOI: https://doi.org/10.1007/BF02535553

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