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

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 <= 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.

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-potent01310nas a2200181 4500008004100000022001400041245018100055210006900236260000800305300001400313490000700327520058500334100002400919700001900943700001900962700002600981856012101007 2025 eng d a1359-734500aInterrupted borrowing hydrogen strategy enabled aminomethylation and direct cross-dehydrogenative coupling strategy enabled dicarbonylation reactions of imidazo[1,5-a]pyridines0 aInterrupted borrowing hydrogen strategy enabled aminomethylation cFEB a3021-30240 v613 a

Herein, we disclose the development of novel aminomethylation and dicarbonylation reactions of imidazo[1,5-a]pyridines. The developed aminomethylation strategy involves a Pd-catalyzed interrupted borrowing hydrogen strategy by utilizing MeOH as the methylene source. A wide variety of imidazo[1,5-a]pyridines and secondary amines were explored for the developed strategy. The established imidazo[1,5-a]pyridine dicarbonylation strategy involves a catalyst/additive-free direct cross-dehydrogenative coupling reaction between imidazo[1,5-a]pyridines and 2-oxoaldehydes.

1 aMahajan, Shivangani1 aBag, Debojyoti1 aKour, Harpreet1 aSawant, Sanghapal, D. uhttps://library.ncl.res.in/content/interrupted-borrowing-hydrogen-strategy-enabled-aminomethylation-and-direct-cross02186nas a2200241 4500008004100000022001400041245017800055210006900233260000800302300001100310490000800321520130800329653003101637653001201668653002101680653001701701100001701718700002101735700001901756700002601775700001901801856012401820 2026 eng d a0045-206800aElucidating the potential of novel class biphenyl-phenyl acetate, IDD-AN-A1, an inhibitor targeting Isocitrate Lyase in Mycobacterium tuberculosis: a target to lead approach0 aElucidating the potential of novel class biphenylphenyl acetate  cMAR a1095570 v1703 a

Isocitrate lyase (ICL), a pivotal enzyme of the glyoxylate shunt pathway in Mycobacterium tuberculosis (Mtb), represents an attractive target for the development of new anti-tuberculosis (TB) therapeutics. In this study, we identified 2-methoxy-4-((nitrosooxy)methyl)phenyl 2-(2-fluoro-[1,1 `-biphenyl]-4-yl)propanoate (IDDAN-A1) as a potent inhibitor of Mtb ICL. The compound exhibited strong activity against Mtb, with a minimum inhibitory concentration of 6.25 mu g/mL, and demonstrated potent inhibition in enzyme-based assays targeting ICL. Molecular docking studies further supported Mtb ICL as the potential molecular target of this compound. Cytotoxicity and hemolytic assays revealed a favorable safety profile for the compound with selectivity index >10. In combination studies, it exhibited additive and synergistic activity with the frontline drug Rifampicin and Delamanid respectively. Additionally, ex vivo assays simulating the intracellular environment of the pathogen demonstrated strong inhibitory potency. In vitro inhibition studies further confirmed the bacteriostatic nature of the compound across different concentrations. Collectively, these findings demonstrate that this molecule possesses promising anti-tuberculosis activity by targeting the ICL enzyme in Mtb.

10aAnti-tuberculosis activity10aEx vivo10aIsocitrate lyase10atuberculosis1 aNegi, Anjali1 aPerveen, Summaya1 aKour, Harpreet1 aSawant, Sanghapal, D.1 aSharma, Rashmi uhttps://library.ncl.res.in/content/elucidating-potential-novel-class-biphenyl-phenyl-acetate-idd-a1-inhibitor-targeting