1,3‐diarylpyrazolones as potential anticancer agents for non‐small cell lung cancer: Synthesis and antiproliferative activity evaluation

Abstract

A series of pyrazolone compounds with different substitution patterns have been synthesized using microwave-assisted methods and evaluated their in vitro antiproliferative activity against human lung adenocarcinoma cell lines (A549 and NCI-H522). Among the tested compounds, the pyrazolone P7 exhibited high antiproliferative activity against both A549 and NCIH522 cancer cell lines while being 10 times less cytotoxic to non-cancerous cells. Moreover, our compounds P7 and P11 exhibited higher antiproliferative activity and selectivity against A549 and NCIH522 cells compared with the clinically approved drugs Afatinib and Gefitinib. The cell cycle analysis showed that the compound P7 and P11 arrests the cell cycle at G0/G1 phase, whereas the compounds P13 and P14 involved in G2/M phase arrest. The results from antiproliferative activity screening, cell cycle analysis, and kinase profiling indicate that the suitably substituted 1,3-diarylpyrazolones exhibit high antiproliferative activity against non-small cell lung cancer cells.

Synthesis, in silico modelling, and in vitro biological evaluation of substituted pyrazole derivatives as potential anti-skin cancer, anti-tyrosinase, and antioxidant agents

“…The microwave-assisted approach was found to be more efficient for pyrazoles P1 – P6 as compared to the cobalt-catalysed approach 89 . In fact, microwave irradiation facilitates the polarisation of the substrate molecules, accelerating the reactions and providing higher product yields than conventional heating procedures.…”

“…A set of 1,3-disubstituted pyrazolones ( P20 – P25 ) were synthesised from β-ketoesters and phenylhydrazine using our recently reported procedure 89 . The pyrazolone P20 is a mono-aryl pyrazolone, whereas P21 – P25 are diaryl pyrazolones.…”

“…Compensating with higher applied concentrations can, for many available agents, result in skin irritation, or severe local or even systemic side effects and other safety concerns 85–88 . As part of our effort to discover new synthetic scaffold-based entities with low toxicity, enhanced efficacy, and improved biopharmaceutic profiles against cutaneous cancers, pigmentation disorders, and various other dermal pathologies, we recently synthesised 1,3-diarylpyrazolones having potent suppressive activity against non-small-cell lung cancer cells 89 .…”

Pyrazolone-type compounds (part II): in vitro and in silico evaluation of antioxidant potential; structure–activity relationship

“…4 Such an outcome was triggered by the diversity of pyrazolone-based compounds and their richness in benecial biological virtues. 2,7 Pyrazolonecored derivatives mostly wield antimicrobial, [8][9][10][11][12][13] anticancer, 7,12,14,15 antiproliferative, 14,16 and antiinammatory potency, [17][18][19][20][21][22] but they were also identied as analgesics, 18,22,23 antivirals, [24][25][26] hypoglycaemics, 27 and antioxidants. 11,28,29 The utilisation of pyrazolone synthon produced numerous hybrid molecules acting as multitarget agents.…”