Synthesis, Characterization and In Vitro Antiproliferative Effects of Novel 5-Amino Pyrazole Derivatives against Breast Cancer Cell Lines

Hanumegowda      Raju; Siddappa      Chandrappa; Doddakunche      S. Prasanna; Hanumappa      Ananda; Tandaga      S. Nagamani; Sonnahallipura      M. Byregowda; Kanchugarakoppal      S. Rangappa

doi:10.2174/157489211795328459

Abstract

In search of synthetic chemotherapeutic substances capable of inhibiting, retarding, or reversing the process of multistage carcinogenesis, we synthesised a series of novel 1-(4-methoxybenzyl)-3-cyclopropyl-1H-pyrazol-5-amine derivatives 9(a-h) by a nucleophilic substitution reaction and characterized by ¹H and ¹³C nuclear magnetic resonance (NMR), liquid chromatography mass spectrometry (LC/MS), Fourier-transform infrared (FTIR), and elemental analysis. These novel compounds were evaluated for their efficacy in inhibiting VERO normal and MCF-7 breast cancer cells proliferation by trypan blue exclusion assay, MTT assay, [³H] thymidine incorporation assay and DNA fragmentation analysis. Among the series, some compounds exhibited interesting growth inhibitory effects against cell lines. From the Structure-Activity Relationship studies, it has been revealed that, both novel patented compounds and therapeutic protocols of N-terminal pyrazole ring structures play key role in the antiproliferative activity.

Keywords: 5- Amino pyrazole derivatives, aryl sulfonamide, breast cancer cells, cell proliferation, cyclisation, [3H] thymidine incorporation, trypan blue exclusion assay, vero normal cells, MTT assay, DNA fragmentation analysis