Synthesis and Studies on Some New Fluorine Containing Hydroxypyrazolines and 1H Pyrazoles-as Possible Antiproliferative Agents

摘要

A series of twenty four newly synthesized l-aroyl-3-aryl-5-hydroxy-5-(2,4-dichloro-5-fluorophenyl) pyrazolines (3) and lH-3-aryl-5-hydroxy-5-(2,4-dichloro-5-fluorophenyl)-pyrazoles (6) were tested for cytostatic and cytotoxic effects on in a primary three cell line-one dose anticancer assay against NCI-H 460 (Lung), MCF 7(Breast) and SF 268 (CNS). Proliferation of these cancer cell lines was strongly inhibited by eleven compounds. These eleven compounds were then passed on for evaluation in the full panel of 60 cell lines derived from seven cancer types namely, Lung, Colon, Melanoma, Renal, Ovarian, CNS and Leukemia. These compounds showed antiproliferative activity on the whole cell panel. Compound lH-pyrazole, 6d [3,4-methylenedioxy at C 3] showed highest activity with Growth Inhibition (GIS0) value <10 uM against all tested 60 cell lines except for Leukamia CCRF-CEM, HL-60TB, K-562 cell lines. Whereas hydroxypyrazolines 3i, 3k 3m, 3o, 3p and 3q showed moderate activity with GI50 value <50 uM against all tested 60 cell lines. Compounds 3h, 3c, 6c appear to be less active with GI50 value >100 uM for some of the tested cell lines. Compound 6a appears to be least active with GI50 value >100 uM for almost all the tested cell lines. The Total Growth Inhibition (TGI) and Lethal Concentration (LC50) values for the most active compound [6d] found to be >100 uM for Leukemia cell lines and for the other cell lines these values remain <20 uM and hence prove to be a cytostatic and cytotoxic for these lines. Hence these newly synthesized pyrazole and pyrazoline derivatives showed promising antiproliferative property.