The enhancement of bacterial resistance of pathogens to currently available antibiotics constitutes a serious public health threat. So, intensive efforts are underway worldwide to develop new antimicrobial agents. To identify compounds with a potent antimicrobial profile, we designed and synthesized low molecular weight 2-mercaptobenzothiazole derivatives 2a-2l and 3a-3l. Both series were screened for in-vitro antibacterial activity against the representative panel of Gram-positive and Gram-negative bacteria strains. The biological screening identified compounds 2e and 2l as the most active ones showing an interesting antibacterial activity with MIC values of 3.12 microg/mL against Staphylococcus aureus and 25 microg/mL against Escherichia coli, respectively. The replacement of the S-H by the S-Bn moiety resulted in considerable loss of the antibacterial action of the 3a-3l series. The antibiotic action of compounds 2e and 2l was also investigated by testing their activity against some clinical isolates with different antimicrobial resistance profile. Moreover, the involvement of the NorA efflux pump in the antibacterial activity of our molecules was evaluated. Finally, in this paper, we also describe the cytotoxic activity of the most interesting compounds by MTS assay against HeLa and MRC-5 cell lines.
2‐Acetylbenzonitriles have been conveniently synthesized by the oxidation of the respective 2‐ethylbenzonitriles, combining in a one‐pot procedure radical bromination and hydrolysis reactions. The obtained ketones reacted under very mild conditions with carbon and hetero nucleophiles to give a wide range of 3,3‐disubstituted isoindolinones in yields of 80–99 % by a tandem process consisting of an addition step and a subsequent Dimroth‐type rearrangement. Among the tested nucleophiles, the addition of water in the presence of a catalytic amount of KOH allowed a convenient access to an unprecedented variety of novel 3‐hydroxy‐3‐methylisoindolinones.
SummaryNew bifunctional chiral ammonium salts were investigated in an asymmetric cascade synthesis of a key building block for a variety of biologically relevant isoindolinones. With this chiral compound in hand, the development of further transformations allowed for the synthesis of diverse derivatives of high pharmaceutical value, such as the Belliotti (S)-PD172938 and arylated analogues with hypnotic sedative activity, obtained in good overall total yield (50%) and high enantiomeric purity (95% ee). The synthetic routes developed herein are particularly convenient in comparison with the current methods available in literature and are particularly promising for large scale applications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.