ABSTRACT
Cancer has been established as the "Emperor of all maladies". In recent years, medicinal chemistry has focused on identifying novel anti-cancer compounds; though discovery of these compounds appears to be a herculean task. In present study, we synthesized forty pyrazolochalcone conjugates and explored their cytotoxic activity against a panel of sixty cancer cell lines. Fifteen conjugates of the series showed excellent growth inhibition (13b-e, 13h-j, 14c-d, 15 a, 15 c-d, 16b, 16d and 18f; GI50 for MCF-7: 0.4-20 µM). Conjugates 13b, 13c, 13d, 16b and 14d were also evaluated for their cytotoxic activity in human breast cancer cell line (MCF-7). The promising candidates induced cell cycle arrest, mitochondrial membrane depolarization and apoptosis in MCF-7 cells at a 2 µM concentration. Furthermore, inhibition of PI3K/Akt/mTOR pathway-regulators such as PI3K, p-PI3K, p-AKT, and mTOR were observed; as well as upregulation of p-GSK3ß and tumor-suppressor protein, PTEN. Our study indicates that pyrazolochalcone conjugates could serve as potential leads in the development of tailored cancer therapeutics.