Facile Synthesis of 5-Bromo--Alkylthiophene-2-Sulfonamides and Its Activities Against Clinically Isolated New Delhi Metallo--Lactamase Producing ST147.

INTRODUCTION

New Delhi Metallo--lactamase producing (NDM-1-KP) sequence type (ST) 147 poses a significant threat in clinical settings due to its evolution into two distinct directions: hypervirulence and carbapenem resistance. Hypervirulence results from a range of virulence factors, while carbapenem resistance stems from complex biological mechanisms. The NDM-1-KP ST147 clone has emerged as a recent addition to the family of successful clones within the species.

METHODS

In this study, we successfully synthesized 5-bromo--alkylthiophene-2-sulfonamides () by reacting 5-bromothiophene-2-sulfonamide () with various alkyl bromides () using LiH. We also synthesized a series of compounds () from compound () using the Suzuki-Miyaura cross-coupling reaction with fair to good yields (56-72%). Further, we screened the synthesized molecules against clinically isolated New Delhi Metallo--lactamase producing ST147. Subsequently, we conducted in-silico tests on compound against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I.

RESULTS

The compound () with favourable drug candidate status, MIC of 0.39 μg/mL, and MBC of 0.78 μg/mL. This low molecular weight compound exhibited the highest potency against the resistant bacterial strains. The in-silico tests revealed that the compound against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I demonstrated H-bond and hydrophobic interactions.

CONCLUSION

The 5-bromo--alkylthiophene-2-sulfonamides displayed antibacterial efficacy against New Delhi Metallo--lactamase producing ST147. After the in-vivo trial, this substance might offer an alternative therapeutic option.