Novel Substituted Imidazo[2,1‐b][1,3,4]Thiadiazole Derivatives: Synthesis, Characterization, Molecular Docking Study, and Investigation of Their In Vitro Antifungal Activities

Abstract

In this study, a new series of substituted imidazo[2,1‐b][1,3,4]thiadiazole derivatives were synthesized. To this end, first 2‐amino‐1,3,4‐thiadiazole derivatives (compounds 2a and 2b), the starting materials, were synthesized with high yields (82% and 79%, respectively). Then imidazo[2,1‐b][1,3,4]thiadiazole derivatives (4–16), the target compounds, were synthesized from reactions of 2‐amino‐1,3,4‐thiadiazole derivatives (2a and 2b) with 2‐bromoacetophenone derivatives (3a–3i) (in yields of 52% to 71%). All of the synthesized compounds were characterized by 1H NMR, 13C NMR, Fourier transform infrared, elemental analysis, mass spectroscopy, and X‐ray diffraction analysis (compounds 4–12, 14, and 15) techniques. In vitro antifungal activity tests were performed for all of the synthesized compounds. Inhibition zones, percentage of inhibition, minimum fungicidal activity, minimum inhibitory concentration, and lethal dose values of the target compounds were determined against some plant pathogens. According to the results of the biological activity tests, all of the synthesized compounds showed moderate to high levels of antifungal activity. Theoretical calculations were performed to support the experimental results. The geometric parameters of selected compounds (5, 6, and 8) were optimized using the density functional theory B3LYP/6‐31G(d) method in the Gaussian 09W package program, and the frontier molecular orbitals (highest occupied molecular orbital–lowest unoccupied molecular orbital) were calculated theoretically. Finally, molecular docking studies were performed for antifungal activity studies of the selected compounds and to determine whether or not these compounds could be inhibitor agents for the 2RKV protein structure.

Synthesis, structural characterization, biological activity, and theoretical studies of some novel thioether‐bridged 2,6‐disubstituted imidazothiadiazole analogues

“…13 C NMR carbon data of the compounds, which were highly consistent with the literature, can be found in the Experimental part of this study, in detail. [1,[35][36][37] Additionally, the mass spectra of all of the synthesized compounds in the study were observed as expected and were supported by the molecular ion peaks. The spectroscopic data for all of the synthesized compounds are given in detail in Experimental section and the relevant spectra are given in Supplementary Material section.…”

“…Compounds 4 and 5 were synthesized according to a method given in the literature. [33][34][35][36] 2-Amino-1,3,4-thiadiazole derivatives (4 and 5) (4 mmol) were dissolved with ethyl alcohol (50 mL) in a 100-mL 2-necked flask. Next, phenacyl bromide derivatives (6a-6i) (4 mmol) were dissolved with absolute ethyl alcohol and added to this solution dropwise using a dropping funnel.…”

“…The 2,6-dichlorobenzylbromide (1), 2,6-difluoro benzylbromide (2), and 5-amino-1,3,4-thiadiazole-2-thiol (3) were obtained by commercially, while the 2-amino-1,-3,4-thiadiazole derivatives (4-5) were obtained as specified in the literature. [33][34][35][36] In the Fourier transform infrared (FTIR) spectra of the 2-amino-1,3,4-thiadiazole derivatives (4-5), symmetric and asymmetric stretching bands that corresponding to the NH 2 group were observed as 2 separate bands at 3271 and 3074 cm −1 . The C N group stretching bands at the thiadiazole ring were observed at 1626 and 1616 cm −1 .…”

“…The 2-amino-1,3,4-thiadiazole derivatives (4 and 5) were observed to be present in the amine-imine tautomeric form in these reactions. [1,[35][36][37]39] In this tautomeric structure, the lone pair electron located on the NH in the imine form, acted as a nucleophile and was replaced by the bromine in the phenacyl bromide derivatives. The hydrogen bromide salt of the target compounds was then formed by a nucleophilic attack of the lone pair electron in the other NH group on phenacyl carbonyl and water separation.…”

Synthesis and Antibacterial Activity Evaluation of Imidazole Derivatives Containing 6‐Methylpyridine Moiety

“…In a review of the literature, compounds containing imidazo[2,1‐ b ][1,3,4]thiadiazole structure are reported to show a variety of biological activities, such as antibacterial, [4–10] anti‐inflammatory, [11–14] anticonvulsant, [15–18] antifungal, [19–22] anti‐tuberculosis, [23–26] anti‐cancer, [27–31] anesthesia, and diuresis activities [32] . Hakan et al [33] .…”