New 1,2,3-Triazole-Containing Hybrids as Antitumor Candidates: Design, Click Reaction Synthesis, DFT Calculations, and Molecular Docking Study

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 3; p. 708
• Main Authors: El Azab, Islam H, El-Sheshtawy, Hamdy S, Bakr, Rania B, Elkanzi, Nadia A A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 29-01-2021; MDPI AG
• Subjects: 1,2,3-triazole; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; antitumor activity; Cell Proliferation - drug effects; Click Chemistry; Cycloaddition Reaction; Density Functional Theory; ErbB Receptors - genetics; Gene Expression Regulation, Neoplastic - drug effects; Hep G2 Cells; Humans; molecular docking; Molecular Docking Simulation; Neoplasms - drug therapy; pyrazole; Structure-Activity Relationship; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - pharmacology; DFT calculation; cycloaddition reaction; molecular docking; antitumor activity; pyrazole; click chemistry; 1,2,3-triazole
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26030708

In an effort to improve and achieve biologically active anticancer agents, a novel series of 1,2,3-triazole-containing hybrids were designed and efficiently synthesized
the Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction of substituted-arylazides with alkyne-functionalized pyrazole-[1,2,4]-triazole hybrids. The structure geometry of these new clicked 1,2,3-triazoles was explored by density functional theory (DFT) using the B3LYP/6-311++G(d,p) level; also, the potential activity of the compounds for light absorption was simulated by time-dependent DFT calculations (TD-DFT). The antitumor impacts of the newly synthesized compounds were
estimated to be towards the human liver cancer cell line (HepG-2), the human colon cancer cell line (HCT-116), and human breast adenocarcinoma (MCF-7). Among the tested compounds, conjugate
was the most potent cytotoxic candidate towards HepG-2, HCT-116, and MCF-7, with IC
= 12.22, 14.16, and 14.64 µM, respectively, in comparison to that exhibited by the standard drug doxorubicin (IC
= 11.21, 12.46, and 13.45 µM). Finally, a molecular docking study was conducted within the epidermal growth factor receptor (EGFR) active site to suggest possible binding modes. Hence, it could conceivably be hypothesized that analogies
,
and
could be considered as decent lead candidate compounds for anticancer agents.