Abstract:Cancer is one of the greatest challenges in modern medicine today. Difficult and long-term treatment, the many side effects of the drugs used and the growing resistance to treatment of neoplastic cells necessitate new approaches to therapy. A very promising targeted therapy is based on direct impact only on cancer cells. As a continuation of our research on new biologically active molecules, we report herein the design, synthesis and anticancer evaluation of a new series of N-Mannich-base-type hybrid compounds… Show more
“…In ligands 2, 10, and 5, the 1,2,4-triazine ring made π-π bond with PHE-864 residue of the receptor, whereas in ligand 10, the nitrogen of 1,2,4-triazine ring and ring itself made π-π bond with ASP-863 and LYS-753 residues of the receptor, respectively, and in ligand 9, the nitrogen of amino group and nitrogen of sulfonamide group made a hydrogen bond with SER-783 and ASP-863 residues of the receptor respectively. All selected drugs showed better binding affinities than the standard anti-cancer drug Neratinib in the case of the 7JXH receptor [32]. When the binding attraction to the selected receptors was analyzed, compounds 10, 2, and 3 were the most intriguing ones.…”
One of the biggest problems facing contemporary medicine is cancer. New approaches to therapy are required due to the difficult and prolonged treatment, the numerous adverse properties of the medications employed, and the developing confrontation of neoplastic cells to treatment. Ten 1,2,4-triazine sulfonamide derivatives (1–10) were chosen for the first time in the current work, and their chemical structures were examined by DFT studies. The in silico flexible docking analysis of the chosen receptors involved in cancer development and metastasis (3RHK, 5GTY, 6PL2, and 7JXH) revealed that the selected compounds are the most promising. The binding affinity of compounds 10, 2, 6, and 4 is much better than the standard drug, Erlotinib, whereas compounds 9, 3, 1, and 7 showed better affinities as compared to standard drugs Neratinib and Tepotinib in the case of 3RHK receptor. The binding affinity against the 5GTY receptor of compounds 10, 5, and 3 is much better than the standard drug Tepotinib, and compounds 7, 6, 2, 4, 1, 8, and 9 showed better than Erlonitib and Neratinib. The binding affinity against the 6PL2 receptor of compounds 8, 3, 5, 4, 9, and 1 is much better than the standard drug Tepotinib. Compounds 10, 6, 7, and 2 were better than Erlotinib and Neratinib. All selected drugs showed better binding affinities than the standard anti-cancer drug Neratinib in the case of the 7JXH receptor, whereas compounds 2, 10, 5, 9, and 8 are better than Erlotinib. In silico ADME experiments supported the identified compounds’ drug similarity. According to the MEP calculations, compounds 3 through 10 can interact non-covalently. The interactions might take the form of σ- and π-hole interactions. Softest compound 4 has the smallest energy gap, with an E-gap value of 3.25 Ev. Compound 4 has the largest energy gap at 3.41 eV. Compound 5 superior electron donor has the highest HOMO energy (6.5470 eV for HOMO). Compound 2 has the lowest LUMO energy, which suggests that it would be the best electron acceptor (ELUMO = 5.766364 eV).
“…In ligands 2, 10, and 5, the 1,2,4-triazine ring made π-π bond with PHE-864 residue of the receptor, whereas in ligand 10, the nitrogen of 1,2,4-triazine ring and ring itself made π-π bond with ASP-863 and LYS-753 residues of the receptor, respectively, and in ligand 9, the nitrogen of amino group and nitrogen of sulfonamide group made a hydrogen bond with SER-783 and ASP-863 residues of the receptor respectively. All selected drugs showed better binding affinities than the standard anti-cancer drug Neratinib in the case of the 7JXH receptor [32]. When the binding attraction to the selected receptors was analyzed, compounds 10, 2, and 3 were the most intriguing ones.…”
One of the biggest problems facing contemporary medicine is cancer. New approaches to therapy are required due to the difficult and prolonged treatment, the numerous adverse properties of the medications employed, and the developing confrontation of neoplastic cells to treatment. Ten 1,2,4-triazine sulfonamide derivatives (1–10) were chosen for the first time in the current work, and their chemical structures were examined by DFT studies. The in silico flexible docking analysis of the chosen receptors involved in cancer development and metastasis (3RHK, 5GTY, 6PL2, and 7JXH) revealed that the selected compounds are the most promising. The binding affinity of compounds 10, 2, 6, and 4 is much better than the standard drug, Erlotinib, whereas compounds 9, 3, 1, and 7 showed better affinities as compared to standard drugs Neratinib and Tepotinib in the case of 3RHK receptor. The binding affinity against the 5GTY receptor of compounds 10, 5, and 3 is much better than the standard drug Tepotinib, and compounds 7, 6, 2, 4, 1, 8, and 9 showed better than Erlonitib and Neratinib. The binding affinity against the 6PL2 receptor of compounds 8, 3, 5, 4, 9, and 1 is much better than the standard drug Tepotinib. Compounds 10, 6, 7, and 2 were better than Erlotinib and Neratinib. All selected drugs showed better binding affinities than the standard anti-cancer drug Neratinib in the case of the 7JXH receptor, whereas compounds 2, 10, 5, 9, and 8 are better than Erlotinib. In silico ADME experiments supported the identified compounds’ drug similarity. According to the MEP calculations, compounds 3 through 10 can interact non-covalently. The interactions might take the form of σ- and π-hole interactions. Softest compound 4 has the smallest energy gap, with an E-gap value of 3.25 Ev. Compound 4 has the largest energy gap at 3.41 eV. Compound 5 superior electron donor has the highest HOMO energy (6.5470 eV for HOMO). Compound 2 has the lowest LUMO energy, which suggests that it would be the best electron acceptor (ELUMO = 5.766364 eV).
“…Strzelecka et al. (2022) synthesized 4,6‐Dimethyl‐N‐{[4‐((4‐(3,4‐dichloro) phenylpiperazin‐1‐yl) methyl)‐5‐sulfanylidene‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl] methyl}‐2‐sulfanylpyridine‐3carboxamide evaluated cytotoxic effect against A375 cells with IC 50 value of 80.79 μM at a concentration of 100 μM. Compound 119 also inhibited colony formation in A375 cell line at two concentrations, 50 and 100 μM shows highest cytotoxic effect among human keratinocytes.…”
Section: Applications Of 134‐oxadiazolesmentioning
The five‐membered 1,3,4‐oxadiazole heterocyclic ring has received considerable attention because of its unique bio‐isosteric properties and an unusually wide spectrum of biological activities. After a century since 1,3,4‐oxadiazole was discovered, its uncommon potential attracted medicinal chemist's attention, leading to the discovery of a few presently accessible drugs containing 1,3,4‐oxadiazole units, and a large number of patents have been granted on research related to 1,3,4‐oxadiazole. It is worth noting that interest in 1,3,4‐oxadiazoles' biological applications has doubled in the last few years. Herein, this review presents a comprehensive overview of the recent achievements in the synthesis of 1,3,4‐oxadiazole‐based compounds and highlights the major advances in their biological applications in the last 10 years, as well as brief remarks on prospects for further development. We hope that researchers across the scientific streams will benefit from the presented review articles for designing their work related to 1,3,4‐oxadiazoles.
“…The research fields explored in this Special Issue include the discovery of new compounds with various biological activities such as: antibacterial 1,2,4-oxadiazole derivatives [ 14 ], antiplasmodial 1,2,5-oxadiazoles [ 15 ], 1,2,4-oxadiazole derivatives as nematicides [ 16 ] and 1,3,4-oxadiazoles with anticancer activity [ 17 ]. Moreover, the synthetic accessibility of bioactive 1,2,4-oxadiazoles at room temperature, was reviewed [ 18 ].…”
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