02215nas a2200241   4500008004100000245019200041210006900233260000800302300001400310490000700324520131200331100001701643700001901660700002001679700001901699700002301718700002301741700001501764700001701779700001901796700002601815856013201841       2025                        eng d00aDiscovery and biological evaluation of nitrofuranyl-pyrazolopyrimidine hybrid conjugates as potent antimicrobial agents targeting Staphylococcus aureus and methicillin-resistant S. aureus0 aDiscovery and biological evaluation of nitrofuranylpyrazolopyrim  cMAR  a1304-13280 v163 a<p>
	Nitrofuran and pyrazolopyrimidine-based compounds possess a broad antimicrobial spectrum including Gram-positive and Gram-negative bacteria. In the present work, a series of conjugates of these scaffolds was synthesized and evaluated for antimicrobial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). Many compounds showed MIC values of &lt;= 2 mu g ml-1, with compound 35 demonstrating excellent activity (MICs: 0.7 and 0.15 mu g ml-1 against S. aureus and MRSA, respectively) and safety up to 50 mu g ml-1 in HepG2 cells. Compound 35 also exhibited no hemolytic activity, biofilm eradication, and effectiveness against efflux-pump-overexpressing strains (NorA, TetK, MsrA) without resistance development. It showed synergistic effects with vancomycin (S. aureus) and rifampicin (MRSA). Mechanistic studies revealed that compound 35 exhibits good membrane-targeting abilities, as evidenced by DAPI/PI staining and scanning electron microscopy (SEM). In an intracellular model, it reduced bacterial load efficiently in both S. aureus and MRSA strains. With a strong in vitro profile, compound 35 demonstrated favorable oral pharmacokinetics at 30 mg kg-1 and potent in vivo anti-MRSA activity, highlighting its potential against antibiotic-resistant infections.</p>
1 aSaini, Sapna1 aReddy, Lakshma1 aGangwar, Anjali1 aKour, Harpreet1 aNadre, Gajanan, G.1 aPandian, Ramajayan1 aPal, Sunny1 aNandi, Utpal1 aSharma, Rashmi1 aSawant, Sanghapal, D.  uhttps://library.ncl.res.in/content/discovery-and-biological-evaluation-nitrofuranyl-pyrazolopyrimidine-hybrid-conjugates-potent