Novel chalcone-derived pyrazoles as potential therapeutic agents for the treatment of non-small cell lung cancer

Abstract

Lung cancer is considered to account for approximately one-fifth of all malignant tumor-related deaths worldwide and is therefore one of the most lethal malignancies. Pyrazole scaffold possesses a wide range of biological and pharmacological activities, which play important roles in medicinal chemistry. The present study reports the synthesis and in vitro biological characterization of nine pyrazoles derived from chalcones as potential anticancer agents for non-small cell lung cancer A-549, H226, and H460 cell lines. Most of the compounds efficiently inhibited the growth of all the tested cancer cell lines at micromolar concentrations. One of the most active compounds (PCH-1) was further evaluated for its effect on cell cycle distribution, apoptosis, migration, epithelial–mesenchymal transition, and oxidative stress. Furthermore, studies on the mechanism of action revealed that PCH-1 disrupts microtubule assembly, leading to cancer cell death. Molecular modeling studies confirmed the potent interaction of PCH-1 with the vinblastine binding site on tubulin. Overall, this study provides novel opportunities to identify anticancer agents in the pyrazole series.

Nucleophilicities of Cyclic α‐Diazo Carbonyl Compounds

“…Reactions of 1 with DMAD gave pyrazoles, which are structural motifs in pharmaceuticals. In particular, N ‐acyl pyrazoles were shown to be selective inhibitors of various hydrolases [26–29] . Thus, the investigated (3+2)‐cycloaddition/[1,5]‐sigmatropic rearrangement cascade may in the future be further exploited to generate bioactive, polycyclic pyrazole derivatives.…”

Novel Thiopyrano[2,3-d]thiazole-pyrazole Hybrids as Potential Nonsulfonamide Human Carbonic Anhydrase IX and XII Inhibitors: Design, Synthesis, and Biochemical Studies

“…Furthermore, hybridization of ethyl 1-phenyl-1 H -benzo­[ d ]­imidazole-2-carboxylate with alicyclic amines yielded benzo­[ d ]­imidazole-2-carboxamides as anti-TB agents and others. − The presence of two or more biologically active pharmacophores within a single unit not only synergizes the biological activity but also enhances the ability to interact with more than one biological target . Moreover, the pyrazole ring system also has a wide range of biological activities, including antifungal, antimicrobial, anticancer, − anti-AIDS, and antidepressants . The pyrazole ring system is an important bioactive ingredient in over-the-counter drugs such as pyrazomycin (anticancer drug), floxan (anti-inflammatory drug), and difenamizole (nonsteroidal anti-inflammatory drug) (Figure ).…”

“… 38 Moreover, the pyrazole ring system also has a wide range of biological activities, including antifungal, 39 antimicrobial, 40 anticancer, 41 − 43 anti-AIDS, 44 and antidepressants. 45 The pyrazole ring system is an important bioactive ingredient in over-the-counter drugs such as pyrazomycin (anticancer drug), floxan (anti-inflammatory drug), and difenamizole (nonsteroidal anti-inflammatory drug) ( Figure 5 ).…”

Targeting AKT2 in MDA‐MB‐231 Cells by Pyrazole Hybrids: Structural, Biological and Molecular Docking Studies

“…The logic of exploring the chalcone stems from the fact that it belongs to important class of bioactive flavonoid family as well as exhibit almost comparable biological and pharmacological activities like pyrazole that include antioxidant, anti‐inflammatory, cytotoxic, antituburcular [26–32] and also inhibit pulmonary carcinogenesis and ovarian cancer cell proliferation [33,34] . Moreover, improved antitumor activity against lung cancer cell is found to be associated with pyrazoles that are derived from chalcone [35,36] . In addition to Pyrazole‐chalcone hybrids, pyrazole pyrazoline hybrids also found to be selective as COX‐2 inhibitors [37,38] while chalcone‐linked pyrazolo [1,5‐a] pyrimidine motifs exhibit antiproliferative activity [39] .…”

“…[33,34] Moreover, improved antitumor activity against lung cancer cell is found to be associated with pyrazoles that are derived from chalcone. [35,36] In addition to Pyrazole-chalcone hybrids, pyrazole pyrazoline hybrids also found to be selective as COX-2 inhibitors [37,38] while chalcone-linked pyrazolo [1,5-a] pyrimidine motifs exhibit antiproliferative activity. [39] Similarly, their interaction with DNA a key target in many cytotoxic compounds, occurs through intercalation, major groove binding, or minor groove binding with improved antitumor activity.…”