In Vitro Antiproliferative Activity of 4-Substituted 2-(2-Hydroxyphenyl)thiazolines on Murine Leukemia Cells

Article abstract of DOI:10.1021/jm00125a018

Two previously synthesized and two structurally novel thiazoline iron chelators are described.N⁴-Benzyl-N¹,N⁸-bis<<2-(2-hydroxyphenyl)thiazolin-4-yl>carbonyl>homospermidine (5) proved to be the most potent antiproliferative and cytocidal compound in the series with in vitro IC 50 values of 3 and 1 μM on L1210 and P388 murine cell lines.The N⁴-acetyl analogue 7 was considerably less active than 5 with IC 50 and cell viability values that were similar to those of the structurally simple thiazolines 2 and 3.The antiproliferative activity of 3 and 7 could be substantially reduced or ablated by delivery to cell suspensions as a 1:1 molar mixture with FeCl3, while the activity of 5 was unaffected by Fe(III) chelation.As expected, 3 induced a G1/S cell cycle block at the 100 μM block consistent with interference with DNA synthesis while 10 μM 5 did not affect L1210 cell cycle distribution.Tritiated thymidine incorporation studies confirmed that 5 was incapable of intefering with DNA synthesis at concentrations below 40 μM.Alkaline elution studies indicate that 5 does not cause DNA strand breaks in vitro at concentrations of 10 μM.The N⁴-benzyl group of 5 appears to impart in vitro potency as the N⁴-acetyl analogue 7 lacks comparable in vitro antiproliferative and cytocidal activity.