Chloramine Trihydrate‐Mediated Tandem Synthesis of New Pyrrole and/or Arene‐Linked Mono‐ and Bis(1,3,4‐Oxadiazole) Hybrids as Potential Bacterial Biofilm and MRSA Inhibitors

Abstract

A two-step tandem protocol was used to prepare new pyrrole and/or arene-linked bis(1,3,4-oxadiazoles) as well as their mono-analogs. The appropriate aldehydes and benzohydrazides were first condensed in ethanol at 80 °C to yield the corresponding N-benzoylhydrazones. Without isolation, the previous intermediates were subjected to a chloramine trihydrate-mediated oxidative cyclization in DMSO at 180 °C to yield the target molecules. The antibacterial potency of the (pyrrole-arene)-linked hybrids exceeded the arene-linked hybrids, and the bis(1,3,4-oxadiazoles) exceeded their mono-analogs against six different ATCC strains. Furthermore, the antibacterial efficacy of bis(1,3,4-oxadiazoles) 11c, and 11f, which are linked to pyrrole, and (p-tolylthio)methyl units, was highest against S. aureus, E. coli, and P. aeruginosa strains. Their MIC ranged between 3.8 and 3.9 μM, while their MBC values ranged between 7.7 and 15.8 μM. Additionally, they showed promising bacterial biofilm inhibitory activity against the same strains tested, with IC 50 values ranging from 4.7 to 5.3 μM. They were also effective against MRSA ATCC : 33591, and ATCC : 43300 strains, with MIC, and MBC values ranging from 3.8-7.9 and 7.7 -15.8 μM, respectively. When tested against the MCF-10A cell lines, hybrids 11c, and 11f are cytotoxic at concEntrations that are more than 6 and 13-fold higher than their MIC values against the S. aureus, E. coli, and P. aeruginosa strains, respectively. This lends support to both hybrids' potential as safe antibacterial agents.

New Arylazo‐Based (Chromene‐Thiazole) Hybrids as Potential MRSA Inhibitors

“…The MBC values of the compounds were evaluated against three strains from the ATCC and two MRSA strains, [56] as described by Sanad et al [67] . (see Electronic supplementary information for more details).…”

“…The MBC values of the compounds were evaluated against three strains from the ATCC and two MRSA strains, [56] as described by Sanad et al [67] (see Electronic supplementary information for more details). The experiment utilized concentrations of the tested derivatives or the reference drugs that ranged from 250 to 0.9 μg/mL.…”

Synthesis of New Pyrazolo[1,5‐a]pyrimidines as Potential Antibacterial Agents: In Vitro and In Silico Study

“…SwissADME prediction of physicochemical properties and drug likeness for the new products. Additional references cited within the Supporting Information [63–65] …”

Synthesis of New Bis(pyrazolo[1,5‐a]pyrimidines) Linked to Different Spacers as Potential MurB Inhibitors

“…Additional references cited within the Supporting Information. [63][64][65] Author Contributions Sherif M. H. Sanad, Alshimaa A. M. Abdelsalam, Aya A. Gamal Eldin and Esraa H. Abdelfattah contributed samples/reagents/ materials/analysis tools, analyzed the data, conceived and designed the experiments. Fatma R. M. Hussein, Nada G. Mohammed, Nariman A. S. Taha, and Ahmed E. M. Mekky performed the experiments, analyzed the data, conceived, designed the experiments and wrote the article.…”