Glabridin-chalcone hybrid molecules: drug resistance reversal agent against clinical isolates of methicillin-resistant Staphylococcus aureusThe authors declare no competing interests.Electronic supplementary information (ESI) available: Tables containing biochemical characterization of various clinical isolates of S. aureus used in the study, antibiotic resistance profile and PCR amplification of mecA gene in clinical MRSA strains. See DOI: 10.1039/c5md00527b

• Main Authors: Kapkoti, Deepak Singh, Gupta, Vivek Kumar, Darokar, Mahendra Padurang, Bhakuni, Rajendra Singh
• Format: Journal Article
• Published: 20.04.2016
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c5md00527b

A novel series of glabridin-chalcone hybrid molecules (GCHMs) were synthesized and evaluated for their antibacterial and resistance reversal activity against clinical isolates of a methicillin-resistant strain of Staphylococcus aureus (MRSA) alone and in combination with norfloxacin. Glabridin showed significant anti-staphylococcal activity against various MRSA clinical isolates with MICs of 12.5 μg ml −1 . However, all its synthesized derivatives displayed moderate to weak activity (MICs ranging from 12.5 to >100 μg ml −1 ). Among all the synthesized hybrid molecules, compounds 6f , 6h , 8f and 8h along with glabridin were chosen for combination study with norfloxacin. Among all tested compounds, 8h exhibited marked synergism and up to 16-fold reduction in MICs with norfloxacin (FICI range from 0.312 to 0.375). In a systemically infected Swiss albino mice model, compound 8h significantly ( p < 0.01, p < 0.05) lowered the systemic bacterial load in blood, liver, kidney, lung and spleen tissues. The present study reports the potential use of GCHMs in the development of economical anti-infective combinations for the treatment of infection caused by clinical MRSA isolates. 16 folds reduction in MICs with norfloxacin against various clinical isolates of MRSA (FICI range from 0.312-0.375).