Synthesis, antimicrobial, and anti-inflammatory activity, of novel S-substituted and N-substituted 5-(1-adamantyl)-1,2,4-triazole-3-thiols

Abstract

The reaction of 5-(1-adamantyl)-4-phenyl-1,2,4-triazoline-3-thione (compound 5) with formaldehyde and 1-substituted piperazines yielded the corresponding N-Mannich bases 6a–f. The reaction of 5-(1-adamantyl)-4-methyl-1,2,4-triazoline-3-thione 8 with various 2-aminoethyl chloride yielded separable mixtures of the S-(2-aminoethyl) 9a–d and the N-(2-aminoethyl) 10a–d derivatives. The reaction of compound 5 with 1-bromo-2-methoxyethane, various aryl methyl halides, and ethyl bromoacetate solely yielded the S-substituted products 11, 12a–d, and 13. The new compounds were tested for activity against a panel of Gram-positive and Gram-negative bacteria and the pathogenic fungus Candida albicans. Compounds 6b, 6c, 6d, 6e, 6f, 10b, 10c, 10d, 12c, 12d, 12e, 13, and 14 displayed potent antibacterial activity. Meanwhile, compounds 13 and 14 produced good dose-dependent anti-inflammatory activity against carrageenan-induced paw edema in rats.

Conjugated Pt(II) Complexes as Luminescence-Switch-On Reporters Addressing the Microenvironment of Bacterial Biofilms

“…coli biofilms (Figure S102, Supporting Information). This outcome can be ascribed to the hydrophobic ada moieties, which effectively interact with the membrane of Gram – bacteria, in good agreement with previous reports. , …”

“…After lysis and centrifugation, the emission from P/ada was found mostly in the sedimented pellet ( F3 P/ada , Figure c). This suggests that the complex only interacts superficially with the cell membrane through the ada groups, in agreement with previous reports, as this moiety can interact with specific receptors and ion channels. , For M/E- t bu , however, the luminescence was detected in both fractions ( F2 M/E‑ t bu and F3 M/E‑ t bu , Figure d). This outcome can be attributed to the interaction of the maltohexaose moiety with the maltodextrin transport system.…”

Structural Insights and Docking Analysis of Adamantane-Linked 1,2,4-Triazole Derivatives as Potential 11β-HSD1 Inhibitors

“…Compounds 1, 2 and 3 were prepared as outlined in Scheme 1 [28], starting with adamantane-1-carbohydrazide A via reaction with phenyl isothiocyanate to yield the thiosemicarbazide analogue B, which was cyclized to the triazole analogue C. Compound C was subsequently reacted with 4-nitrobenzyl bromide, 4-fluorobenzyl chloride or 4chlorobenzyl chloride in N,N-dimethylformamide (DMF) in the presence of potassium carbonate to yield the target compounds 1-3. Single crystals suitable for X-ray diffraction were obtained by slow evaporation of a solution of the compounds in EtOH/CHCl 3 (1:2, v/v) at room temperature.…”

“…In continuation of ongoing interest in the structural studies and potential biological applications of adamantane-based derivatives [ 23 , 24 , 25 , 26 , 27 , 28 ], we report herein the crystal structure, Hirshfeld surface analysis, pairwise interaction energies and electronic properties of three adamantane-linked triazole derivatives 1 – 3 . Molecular docking experiments at the 11β-HSD1 active site were also performed in order to predict the potential 11β-HSD1 binding affinity and binding interactions of the compounds.…”

“…Thus, the development of selective 11β-HSD1 inhibitors would be an important therapy for non-insulin-dependent diabetes, hyperglycemia, obesity, insulin resistance, hyperlipidemia, hypertension and other symptoms associated with excessive body cortisol [20][21][22]. In continuation of ongoing interest in the structural studies and potential biological applications of adamantane-based derivatives [23][24][25][26][27][28], we report herein the crystal structure, Hirshfeld surface analysis, pairwise interaction energies and electronic properties of three adamantane-linked triazole derivatives 1-3. Molecular docking experiments at the 11β-HSD1 active site were also performed in order to predict the potential 11β-HSD1 binding affinity and binding interactions of the compounds.…”