Design, Synthesis, Characterization, Antiproliferative Activity, and In Silico Studies of Novel Alkyl Ether Derivatives Containing 1H‐1,2,4‐Triazole Ring

Abstract

In this study, starting from 1H-1,2,4-triazole, a new series of aliphatic ether derivatives containing phenyl and 1H-1,2,4triazole groups together were synthesized using reduction and Williamson ether synthesis mechanisms, respectively. The molecular structures of the synthesized compounds were characterized by fourier-transform infrared spectroscopy (FT-IR), 1 H and 13 C nuclear magnetic resonance ( 1 H NMR and 13 C NMR), mass spectroscopy, and elemental analysis techniques. All synthesized compounds were screened against three different human cancer cell lines, including colon, lung, and liver cancer cells. Some of the compounds showed exceptionally high antiproliferative effects against all three cancer cell lines, with IC 50 values much lower than the positive control drug bendamustine. In addition, molecular docking studies were performed to support the in vitro results and the interaction types and amino acids that play key roles in the binding of the compounds to enzymes were identified. Finally, the potential of these compounds to be drugs and their drug-likeness properties were evaluated by absorption, distribution, metabolism, and excretion-toxicity (ADMET) calculations and it was determined that the compounds could be drug candidates with the capacity to be effective and safe drugs for use in the treatment of different diseases.

Imidazole-Derived Alkyl and Aryl Ethers: Synthesis, Characterization, In Vitro Anticancer and Antioxidant Activities, Carbonic Anhydrase I–II Inhibition Properties, and In Silico Studies

“…The most significant evidence indicating the formation of the suggested compounds in the 1 H NMR spectra of these compounds is the disappearance of the –OH proton peaks observed as a broad singlet in the range of 4.83–4.75 ppm and the increase in peak intensity in the aliphatic region (1–5 ppm range) for compounds 7 – 15 and in the aromatic region (6.5–8.00 ppm) for compounds 16 – 24 . These data are in excellent agreement with similar studies in the literature. − , …”

“…These data are in excellent agreement with similar studies in the literature. [65][66][67]71 The carbon peaks observed in the aliphatic region (60−10 ppm range) for compounds 7−15 and in the aromatic region (140−115 ppm range) for compounds 16−24 in the 13 C NMR spectra of the target compounds match the carbon counts of the proposed structures. Finally, the molecular ion peaks of the target compounds were observed as expected in the mass spectra, confirming the structures using all the spectroscopic methods used.…”

“…In the first step, ketone derivatives ( 3a – c ) were synthesized with varying yields between 51 and 62% by the reaction of imidazole ( 2 ) with various phenacyl bromide derivatives ( 1a – c ) in the presence of triethylamine, as described in the literature. , In this reaction, the proton of imidazole is removed by triethylamine in an acetone medium. Subsequently, a nucleophilic center, with a partially positive carbon atom, undergoes an SN 2 -type substitution reaction by attack from behind.…”