Semi-synthesis of β-keto-1,2,3-triazole derivatives from ethinylestradiol and evaluation of the cytotoxic activity

Abstract

In this study, we report our contribution to the application of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction for the synthesis of β-keto-1,2,3-triazole derivatives 3a-f from ethinylestradiol and their application in the inhibition of two human cancer cells lines: human breast adenocarcinoma (MCF-7) and human hepatocellular carcinoma (HepG2). The β-keto-1,2,3-triazole derivates 3a-f exhibited moderate cytotoxic activity for the HepG2 cells with IC50 values of 29.7 μM (3a), 16.4 μM (3b), 17.8 μM (3c), 20.4 μM (3d), 28.1 μM (3e) and 28.2 μM (3f). The semi-synthetic β-keto-1,2,3-triazoles derivatives 3a-f were all characterized by FT-IR, NMR, HRMS and [α]D.

Design, Synthesis, Molecular Modeling, Anticancer Studies, and Density Functional Theory Calculations of 4-(1,2,4-Triazol-3-ylsulfanylmethyl)-1,2,3-triazole Derivatives

“…Furthermore, the speed and accuracy of the molecular docking approaches have been enhanced and these methods now play a noteworthy role in structure-based drug design. The newly synthesized hybrids were gauged using in silico docking studies for acquiring an additional apprehension of the binding pattern of the target ligands with the cyclin-dependent kinase 2 (CDK2), whose overexpression causes dysfunction of the cell cycle, which is thoroughly allied with hyperproliferation of cancer cells. − Numerous evidences have been put forward in the literature sustaining the concept of restraining cancer progression by aiming CDK2. − In various categories of human tumors, the dysregulation of CDK2 is noticed, thereby for anticancer therapy, making CDK2 a promising drug target. ,− In breast cancer progression, CDK2 is considered accountable for activating and phosphorylating the receptor hormones. CDK2 structure with Protein Data Bank (PDB) ID: 2R3I was recruited for carrying out molecular docking studies owing to its higher resolution (1.28 Å) and nonmutated monomeric form.…”

Room-Temperature Cu(II) Radical-Triggered Alkyne C–H Activation

“…Copper-catalyzed alkyne azide cycloaddition reactions have been used to develop triazole derivatives of ethinylestradiol. Related derivatives have cytotoxic activity against human cancer cell lines and can act as positron emission tomography (PET) imaging agents for estrogen receptor positive (ER + ) breast cancer. , To demonstrate the powerful scope of our catalyst in an A 3 reaction, 1 was employed in the synthesis of a propargylamine steroid derivative, 2p , which was isolated in good yield as a white solid. Other pharmaceutically relevant examples include A 3 reactions on a (BRD4) bromodomain inhibitor JQ1 analogue, to afford 2q , and on the clinically used epidermal growth factor receptor kinase inhibitor erlotinib, to afford 2r .…”

Design and synthesis of cabotegravir derivatives bearing 1,2,3-triazole and evaluation of anti-liver cancer activity

“…A research group used ethynyl estradiol as the parent nucleus and obtained a series of compounds containing the 1,2,3-triazole structure through the click chemistry reaction, which had moderate inhibitory effects on HepG2 cells. Among them, compound 2 had an IC 50 value of 17.8 μM for HepG2 cells ( Queiroz et al, 2019 ). Another research group synthesized a series of pyrrolo [2,3-d] pyrimidine and pyrazolo[3,4-d] pyrimidine derivatives bearing 1,2,3-triazole, which had good inhibitory effects on HepG2 cells.…”