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.

In this study, starting from 2‐amino‐1,3,4‐thiadiazole derivatives (3–5), a new series of 2,6‐disubstituted (compounds 7–15) and 2,5,6‐trisubstituted (compounds 16–33) imidazo[2,1‐b][1,3,4]‐thiadiazole derivatives were synthesized using cyclization and Mannich reaction mechanisms, respectively. All synthesized compounds were characterized by 1H‐NMR, 13C‐NMR, FT‐IR, elemental analysis, and mass spectroscopy techniques. Also, X‐ray diffraction analysis were used for compounds 4, 7, 11, 17, and 19. The cytotoxic effects of the new compounds on the viability of colon cancer cells (DLD‐1), lung cancer cells (A549), and liver cancer cells (HepG2) were investigated using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) method in vitro. Compound 15 was found to be the most potent anticancer drug candidate in this series with an IC50 value of 3.63 μM against HepG2 for 48 h. Moreover, the absorption, distribution, metabolism, and excretion (ADME) parameters of the synthesized compounds were calculated and thus, their potential to be safe drugs was evaluated. Finally, to support the biological activity experiments, molecular docking studies of these compounds were carried out on three different target cancer protein structures (PDB IDs: 5ETY, 1M17, and 3GCW), and the amino acids that play key roles in the binding of the compounds to these proteins were determined.