Preparation of some novel thiazolidinones, imidazolinones, and azetidinone bearing pyridine and pyrimidine moieties with antimicrobial activity

Abstract

By aiming to design new antimicrobial agents, we prepared new series of thiazolidin‐4‐ones(12a–d), imidazolin‐4‐ones(13a–d), and azetidin‐2‐ones (14a–d), having pyridine and pyrimidine moieties. Chemical structures of these derivatives were elucidated by the use of spectral and elemental analyses. All the new substituted pyridopyrimidines were subjected to in vitro antimicrobial testing by estimating the zone of inhibition toward Bacillus subtilis and Staphylococcus aureus, as examples of bacterial species, in addition to Aspergillus flavus and Candida albicans, as examples of fungal species. The results of antimicrobial testing detected that all the screened derivatives displayed antibacterial effect; especially azetidin‐2‐one derivative, (14c), was the most active one. Regarding the antifungal potential, only thiazolidinone derivatives, 12a and 12c, and the imidazolinone, 13c, displayed inhibitory activity toward Aspergillus flavus, while all the tested compounds, 12a–d, 13a–d, and 14a–d, except 14a, produced inhibitory potential toward Candida albicans. Docking studies of the most active antimicrobial agents, 12c, 13c, and 14c, within GLN‐6‐P, recorded good scores with several binding interactions with the active site.

The Bioactivity of Thiazolidin-4-Ones: A Short Review of the Most Recent Studies

“…Compounds 127a-127d generally showed moderate antibacterial and antifungal activities, except Compound 127c. This derivative demonstrated comparable antifungal activity (inhibition zone-14 and 21 mm) with amphoterecin B (inhibition zone-15 and 19 mm) towards A. niger and C. albicans strains, respectively [132]. Other thiazolidine-4-one derivatives, with pyrimidine moiety (128a, 128b) demonstrated good antibacterial activity with MIC in the range of 3.12-12.5 µg/mL against S. aureus, S. epidermidis, E. coli and Proteus mirabilis.…”

Inhibitors of glucosamine-6-phosphate synthase as potential antimicrobials or antidiabetics – synthesis and properties

“…Molecular docking studies based on the GAH domain of GlcN-6-P synthase (pdbid: 1xff) revealed the possible formation of H-bonds with Gly99 and arene-arene interaction with Trp74 located at the active centre. The binding energies for 93 , 95 , and 96 were −13.06, −16.89, and −15.76 kcal/mol, respectively 87 .…”

“…2,4,6-trisubstituted-1,3-diazines 93–96 ( Scheme 22 ) were reported by Bakr and co-workers as promising antimicrobial agents 87 . Synthesis of these compounds started from condensation of an appropriately p -substituted benzaldehyde and 2-(acetylamino)pyridine that gave the α,β-unsaturated product 97 .…”

“…The imine was the starting material for three different cyclisation reactions. Condensation of 98 with 1-chloroacetic acid chloride resulted in the formation of an azetidine-2-on ring of inhibitor 93 , while reactions with 1-mercaptoacetic acid and glycine gave five-membered rings of inhibitors 94–96 , respectively ( Scheme 22 ) 87 . Derivative 93 , possessing azetidine-2-one substituent, occurred to be the most potent antibacterial agent.…”

Antioxidant, Antimicrobial, and Molecular Docking Studies of Novel 1, 4-naphthoquinone Derivatives

“…Glucosamine-6-phosphate synthase enzyme (GlcN-6-P) has been proposed as a promising target for many antimicrobial agents since this enzyme is important for ammonia transferring from L-glutamine to fructose-6-phosphate and then transform by isomerization the produced fructosamine to glucosamine-6-phosphate, which is essential for cell wall formation [54][55][56]. To explore the binding modes of the novel candidates, all these candidates 4-9ad were docked inside the active site of GlcN-6-P using a molecular operating environment (MOE, version 2008.10).…”