Actividad citotóxica en líneas celulares tumorales humanas de 16 derivados tipo bis (espiro-2,4-dihidro-3H-pirazol-3-ona) ciclopropano

Abstract

Abstract: Pyrazole and it s derivatives are heterocyclic compounds widely used for the design of new ATP-competitive CDK inhibitors, which aim to stop the cancer cell cycle. The present work consists in determining the antiproliferative activity in human tumor cell lines (RKO, PC-3, HeLa, A-549 and MCF-7) of 16 derivate of type bis (spiro-2,4-dihydro-3H-pyrazole- 3one) cyclopropane at 100 μM concentrations, as well a calculating the IC50 of the most potent compounds and assessing their cytostatic effect on cell lines that showed sensitivity. The results obtained demonstrate that the 4d, 4k, 4q, 4r and 4s derivatives inhibit cell growth in the RKO, PC-3 and HeLa tumor lines, while the 4e and 6e derivatives in RKO and HeLa. The IC50 range of effective derivatives was 49.79 μM to 114.80 μM, with 4r and 4s derivatives with fluorinated substituents at the R3 position of the aryl being the most potent in the three tumor lines. As for the mechanism of inhibition exerted by the seven derivatives, it was determined by flow cytometry that derivatives 4k, 4q, 4r and 4s induce G0/G1 phase arrest in both RKO and PC-3; however, in the HeLa tumor line derivatives 4q, 4r and 4s acted on the G2/M phase; likewise, 4e and 6e showed cycle arrest in the G0/G1 phase in RKO cells and arrest in the S phase in the HeLa tumor line; while, the 4d derivative showed arrest of the S phase in RKO cells.