(S)-form of α-methyl-N(α)-phthalimidoglutarimide, but not its (R)-form, enhanced phorbol ester-induced tumor necrosis factor-α production by human leukemia cell HL-60: implication of optical resolution of thalidomidal effects

Article abstract of DOI:10.1248/cpb.42.1157

The rate of racemization of N(α)-phthalimidoglutarimide (thalidomide) was determined as its half life to be 566 min at pH 7.4/37°C. This fast racemization of thalidomide resulted in no apparent difference between (S)- and (R)-forms of the compound on enhancing activity of phorbol ester-induced tumor necrosis factor (TNF)-α production by human leukemia HL-60 cells. Optically pure forms of structurally related analog of thalidomide, (S)- and (R)-α-methyl-N(α)-phthalimidoglutarimides, (methylthalidomides), which do not racemize under the physiological condition, were prepared. Only (S)-form of methylthalidomide, but not its (R)-form, elicited TNF-α production- enhancing effect, suggesting that the (S)-isomer of thalidomide would be the active form in terms of thalidomidal biological response modifying effects.

Full text of DOI:10.1248/cpb.42.1157

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