Synthesis, Anticancer Activity, and Docking Studies of Novel Hydroquinone-Chalcone-Pyrazoline Hybrid Derivatives

• Published in: International journal of molecular sciences Vol. 25; no. 13; p. 7281
• Main Authors: Maldonado, Javier, Oliva, Alfonso, Guzmán, Leda, Molinari, Aurora, Acevedo, Waldo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.07.2024
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; antiproliferative activity; Cancer; Cell cycle; Cell division; Cell Line, Tumor; Cell Proliferation - drug effects; Chalcone - chemistry; Chalcone - pharmacology; Chalcones - chemical synthesis; Chalcones - chemistry; Chalcones - pharmacology; Chemistry; Growth factors; HT29 Cells; Humans; Hydroquinones - chemical synthesis; Hydroquinones - chemistry; Hydroquinones - pharmacology; Kinases; MCF-7 Cells; molecular docking; Molecular Docking Simulation; Pharmaceutical sciences; Polymerization; Proteins; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; pyrazoline-1,4-benzohydroquinone; Structure-Activity Relationship; pyrazoline-1,4-benzohydroquinone; antiproliferative activity; molecular docking
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25137281

A novel series of antitumor hybrids was synthesized using 1,4-benzohydroquinone and chalcone, furane, or pyrazoline scaffolds. This were achieved through isosteric substitution of the aryl group of the chalcone β-carbon with the furanyl moiety and structural modification of the α,β-unsaturated carbonyl system. The potential antitumor activity of these hybrids was evaluated in vivo on MCF-7 breast adenocarcinoma and HT-29 colorectal carcinoma cells, demonstrating cytotoxic activity with IC values ranging from 28.8 to 124.6 µM. The incorporation of furan and pyrazoline groups significantly enhanced antiproliferative properties compared to their analogues and precursors ( - ), which were inactive against both neoplastic cell lines. Compounds , , and exhibited enhanced cytotoxicity against both cell lines, whereas compound 8 showed higher cytotoxic activity against HT-29 cells. Molecular docking studies revealed superior free-energy values (ΔG ) for carcinogenic pathway-involved kinase proteins, with our in silico data suggesting that these derivatives could be promising chemotherapeutic agents targeting kinase pathways. Among all the synthesized PIBHQ compounds, derivatives and exhibited the best drug-likeness properties, with values of 0.53 and 0.83, respectively. ADME results collectively suggest that most of these compounds hold promise as potential candidates for preclinical assays.