Abstract

Background: Indole and pyrazole constitute a major class of biologically active scaffolds. The amalgamation of two or more pharmacophores would generate novel molecular templates that are likely to unveil remarkable biological properties.

Objective: An efficient and high yielding synthesis of indole-pyrazole integrated α-cyano substituted chalcones and their in vitro anti-breast cancer and antioxidant evaluation.

Methods: The synthesis of a series of indole-pyrazole amalgamated α-cyano substituted chalcones (6a-o) was achieved by reacting substituted 3-cyanoacetyl indole 2 with substituted pyrazole aldehyde 5 in the presence of piperidine. All the newly synthesized compounds have been characterized by IR, ¹H NMR and HRMS spectroscopy.

Results: Anti-breast cancer evaluation of the synthesized compounds in vitro against MCF-7 cell line revealed high anti-breast cancer activities. Amongst the compounds screened 6f, 6g, 6h, 6c, 6d, 6e, 6i and 6k unveiled excellent activity against breast carcinoma (GI₅₀ <0.1μM) as good as adriamycin (GI₅₀ <0.1μM). The compounds were also screened against the normal Vero monkey cell line and the results demonstrated more selectivity against MCF-7. On the other hand, compounds 6b, 6c, 6d, 6h and 6i have shown moderate DPPH and NO radical scavenging activity.

Conclusion: Most of the synthesized compounds exhibited significant antitumor activities. These results further support its safety margin by studying the activity on normal Vero monkey cell line. These results acclaim the possible use of these compounds for the design and development of potent anti-breast cancer agents.

Keywords: Indole-pyrazole chalcones, anti-breast cancer, anti-inflammatory, antioxidant, α-cyano, pharmacophores.

Graphical Abstract