Assessment of Dihydro[1,3]oxazine‐Fused Isoflavone and 4‐Thionoisoflavone Hybrids as Antibacterials

Abstract

A series of isoflavone functionalized 3,4‐dihydro‐1,3‐oxazine hybrids was synthesized in good to excellent yields through a Mannich‐type condensation cyclization reaction of 6‐chloro‐7‐hydroxy‐3‐(2‐methoxy‐phenyl)‐chromen‐4‐one or 6‐chloro‐7‐hydroxy‐3‐(2‐methoxy‐phenyl)‐chromene‐4‐thione with formaldehyde and primary amines. After spectroscopic characterization, these newly prepared hybrids were evaluated for their antibacterial activities against two of each Gram positive (Staphylococcus aureus and Bacillus subtilis) and Gram negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains. Among the screened compounds, dihydro[1,3]oxazine‐fused 4‐thionoisoflavones(9 band9 c) exhibited potent inhibitory activity against all the tested bacterial species. Moreover, compound 9 b possessed most promising antibacterial activity against P. aeruginosa and B. subtiliswith MIC 16 μg/mL and S. aureusand E. coliwith MIC 32 μg/mL. Further, 9 bdemonstrated better efficacy (MIC=16 μg/mL) than the standard drug ampicillin (MIC=32 μg/mL) against P. aeruginosaand it also found to be equipotent (MIC=16 μg/mL) as ampicillin against B. subtilis. Considering the disk diffusion and synergistic studies, 9 bemerged asmost active compound showing potent activity against all the tested bacterial strains. In addition, no significant hemolysis or cytotoxicity was observed towards human embryonic kidney (HEK293)cells as well as Galleria mellonellalarvae (in vivo). Hence, compound 9 bhas potential to be further explored alone and in combination with ampicillin as a next generation antibacterial agent.

Synthesis of 1,2,4‐Oxadiazole‐sulfonamide Conjugates and Their Synergistic Effect with Ampicillin as Antimicrobial Agents

“…At 37 °C and 120 rpm, the plates were incubated for overnight. After the completion of the incubation period, the growth was measured by using a Thermo Scientific Multiskan Go plate reader in terms of OD (optical density) at 600 nm [17,18] …”

“…From this culture, approximately 10 5 cells/mL were taken and inoculated into molten nutrient agar medium, which was subsequently poured into 90‐mm diameter Petri plates. After solidification, sterilized 6 mm disks, made of Whatman paper and also 90‐mm in diameter, were carefully placed on the solid agar surface at appropriate distances [11,18,20] . Different concentrations of the test compounds, including 1/2 MIC, MIC, and 2 MIC, were applied to the disks using a stock solution of 10.24 mg/mL.…”

Design, Synthesis and Mechanistic Studies of Novel Isatin-Pyrazole Hydrazone Conjugates as Selective and Potent Bacterial MetAP Inhibitors

“…The 96-well plates were kept in an incubator shaker at 100 rpm for 24 h. The MIC was determined as the lowest concentration that prevented observable cell growth. All experiments were conducted with three biological triplicates [ 45 , 46 ].…”

Development of Oxadiazole-Sulfonamide-Based Compounds as Potential Antibacterial Agents

“…The hemolytic activity of the compounds OX7 and OX11 was studied using human red blood cells ( h RBCs) . The procedures used to perform the hemolytic study were similar to those reported earlier …”

“…55 The procedures used to perform the hemolytic study were similar to those reported earlier. 56 % hemolysis was calculated from the following equation (eq 2).…”