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

Abstract

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 via 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 in vitro 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 7 was the most potent cytotoxic candidate towards HepG-2, HCT-116, and MCF-7, with IC50 = 12.22, 14.16, and 14.64 µM, respectively, in comparison to that exhibited by the standard drug doxorubicin (IC50 = 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 7, 6, and 5 could be considered as decent lead candidate compounds for anticancer agents.

1,2,3‐Triazole hybrids as anticancer agents: A review

“…It was noted that electron-releasing groups in the phenyl ring attached to N-1 of 1,2,3-triazole showed higher cytotoxic potential than those with electron-withdrawing substituents. [66] 1,2,3-Triazole-incorporated pyrazolinyl conjugate 57 showed significant growth inhibition against leukemia CCRF-CEM, colon cancer HCT-15, CNS cancer SF-255, renal cancer CAKl-1, and breast cancer NCI/ADR-RES cell lines, with GI 50 values ranging from 0.6 to 3.37 μM. The lipophilic substituent at position 3 of the pyrazole ring increased activity, whereas bioisosteric replacement of the pyrazole ring with 1,2,3-triazole either abolished or reduced activity.…”

Synthesis and α-Glucosidase Inhibition Activity of 2-[3-(Benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl]-N-arylacetamides: An In Silico and Biochemical Approach

“…In silico screening is an excellent approach for the screening of libraries of compounds in a short time and thus it minimizes the laborious synthetic work [52][53][54][55]. Molecular docking is a widely used method to predict binding interactions between the 3D conformations of various ligands and receptor proteins that helps in optimization and leads toward drug development [56][57][58].…”

Therortical Studies and Investagting of Selected Potnet CDK2 Inhibitors as Anticancer Agents

“…Density functional theory it's a quantum mechanical modeling method where it's applications has a great significance in targeting drug discovery studies especially invention of new anti-cancer agents [17], [18], [19]. Interrupting of DFT calculations aid in create a comprehensive picture about physical and chemical properties such as stability and reactivity toward electrophiles or nucleophiles as well as build a molecular electrostatic map that represents the electropositive and electronegative sites over the chemical structure, polarity, reactivity descriptors etc.…”