Synthesis, Biological Evaluation, Migratory Inhibition and Docking Study of Indenopyrazolones as Potential Anticancer Agents

• Published in: Chemistry & biodiversity Vol. 19; no. 9; pp. e202200399 - n/a
• Main Authors: Hosseini Nasab, Narges, Han, Yohan, Hassan Shah, Fahad, Vanjare, Balasaheb D., Ja Kim, Song
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.09.2022
• Subjects: Acetonitrile; Aldehydes; anticancer; Anticancer properties; antiproliferative; Antitumor activity; Antitumor agents; Biological effects; Cancer; Cell migration; Cell proliferation; Chemical synthesis; Cyclooxygenase-2; Indenopyrazolones; Inflammation; Matrix metalloproteinase; Matrix metalloproteinases; Melanoma; Metalloproteinase; Molecular docking; Optimization; Room temperature; Tumor cell lines; Tyrosinase
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.202200399

Some bioactive derivatives of indeno[1,2‐c]pyrazolones were synthesized through the reaction of phenylhydrazine, different aldehydes and indan‐1,2,3‐trione at room temperature in acetonitrile. Analytical and spectroscopic studies have confirmed the structural characteristics of the synthesized compounds. In addition, the target compounds were screened for the in‐vitro antiproliferative properties against the B16F10 melanoma cancer cell lines by the standard MTT assay. The effect on inflammatory marker cyclooxygenase 2 and matrix metalloproteinase 2, 9 was also checked to determine the anti‐inflammatory and anti‐cell migratory properties of these compounds. The final compounds were also tested for their tyrosinase inhibitory activity. Among all compounds, screened for anticancer activity, three compounds 4e, 4f and 4h reduced the cell proliferation significantly comparable to that of the positive standard drug erlotinib (IC50=418.9±1.54 μM) with IC50 values ranging from 20.72–29.35 μM. The compounds 4c–4h decreased the COX‐2 expression whereas the MMP 2, 9 expressions were significantly reduced by 4a, 4b and 4h. This was confirmed by molecular docking studies, as 4e, 4f and 4h displayed good interactions with the active site of BRAF protein. The compounds 4b, 4f and 4h exhibited moderate tyrosinase inhibition effect as compared to α‐MSH. Collectively, compound 4h can be considered as a candidate for further optimization in the development of anticancer therapies based on the results of biological investigations in this study.