02519nas a2200301 4500008004100000022001400041245009900055210006900154260000800223300001400231490000700245520150600252653002701758653002601785653002501811653003001836653004201866653003001908100001901938700001701957700002201974700001701996700001902013700001902032700002002051700001702071856012902088 2025 eng d a1756-891900aCoumarin hybrids: dual-target candidates for future antimicrobial and antitubercular therapies0 aCoumarin hybrids dualtarget candidates for future antimicrobial  cMAY a1131-11420 v173 a

Aims: This study aimed to synthesize, characterize, and evaluate the antimicrobial and antitubercular activities of two novel series of coumarin-based derivatives (Series 5 and Series 9), focusing on their structure-activity relationship (SAR) and molecular docking interactions with key bacterial enzymes. Materials & methods: Series 5 (5a-5j) and Series 9 (9a-9t) compounds were synthesized and characterized using spectroscopic techniques. Their antimicrobial and antitubercular activities were evaluated against Mycobacterium tuberculosis, Staphylococcus aureus, Bacillus subtilis, and E. coli. IC50 values were determined, and molecular docking studies were conducted to assess binding interactions with M. tuberculosis enoyl-ACP reductase (InhA) and E. coli DNA gyrase B. Results: Series 5 compounds exhibited moderate activity, with 5f, 5 g, 5i, and 5j showing notable inhibition. Series 9 derivatives displayed superior dual-target inhibition, with 9t, 9c, 9a, 9b, and 9p achieving >90% inhibition against S. aureus and B. subtilis. The lowest IC50 against M. tuberculosis was observed for 9c (1.50 mu g/mL), followed by 9a (2.84 mu g/mL) and 9b (2.73 mu g/mL). Molecular docking confirmed strong binding interactions, correlating with observed biological activities. Conclusions: Series 9 compounds, particularly 9t, 9c, and 9a, demonstrate high potential as dual-target antimicrobial drug candidates. Further optimization may enhance their therapeutic efficacy. [GRAPHICS]

10aAntimicrobial activity10aantitubercular agents10aCoumarin derivatives10aMolecular docking studies10astructure-activity relationship (SAR)10athiophene-based compounds1 aBavishi, Abhay1 aVala, Hardev1 aThakrar, Shailesh1 aSwami, Sagar1 aSarkar, Dhiman1 aShukla, Rushit1 aKamdar, Jignesh1 aShah, Anamik uhttps://library.ncl.res.in/content/coumarin-hybrids-dual-target-candidates-future-antimicrobial-and-antitubercular-therapies02287nas a2200289 4500008004100000022001400041245012500055210006900180260000800249300001200257490000700269520132000276653004001596653002701636653002801663653002601691653001001717653001401727653001301741100001901754700001701773700001701790700002201807700001701829700001901846856013201865 2025 eng d a0022-152X00aRegio selective synthesis of pyrazole derivatives of 5-chloro-2-methoxy phenyl hydrazide and their biological evaluation0 aRegio selective synthesis of pyrazole derivatives of 5chloro2met cAPR a325-3290 v623 a

Present study involves synthesis of derivatives of (5-chloro-2-methoxyphenyl) (5-alkyl-3-(substituted) (phenyl/alkyl)-1H-pyrazol-1-yl) methanones. Structural elucidation of the synthesized compounds was depicted by the data of 1H and 13C NMR, IR, and Mass spectral analysis. The newly synthesized compounds 1a-1d and 2a-2i were screened in vitro against Mycobacterium tuberculosis H37Ra using an established XRMA protocol. Among the screened compounds, 2d, 2f, and 2h showed good percent inhibition against the active stage of M. tuberculosis H37Ra 80.77, 55.70, and 79.54, respectively, at 30 mu g/mL of inhibitor concentration. Further in secondary screening, compound 2d exhibited significant antitubercular activity on the active stage of M. tuberculosis H37Ra with IC50 of 0.208 mu g/mL. The synthesized compounds were also screened for antibacterial activity and found no significant activity against Gram-positive Bacteria Bacillus subtitles and Staphylococcus aureus and Gram negative bacteria Pseudomonas aeruginosa and Escherichia coli at 30 mu g/mL, which confirms the specificity of inhibitory activity against M. tuberculosis and more selectively against the active stage. The present study will be helpful for the further development of these molecules into antitubercular lead candidates.

10a5-chloro-2-methoxy phenyl hydrazide10aantibacterial activity10aAntitubercular activity10aBiological evaluation10aH37Ra10ahydrazide10aPyrazole1 aBavishi, Abhay1 aVala, Hardev1 aSwami, Sagar1 aThakrar, Shailesh1 aShah, Anamik1 aSarkar, Dhiman uhttps://library.ncl.res.in/content/regio-selective-synthesis-pyrazole-derivatives-5-chloro-2-methoxy-phenyl-hydrazide-and-their02453nas a2200289 4500008004100000022001400041245013400055210006900189260000800258300001500266490000700281520151600288653000601804653002201810653002301832653002401855653002101879653001301900100001901913700001701932700002101949700001701970700002201987700001902009700001702028856011802045 2025 eng d a2365-654900aSynthesis, biological screening, and molecular docking of hybrid pyrazole scaffolds for antitubercular and antimicrobial activity0 aSynthesis biological screening and molecular docking of hybrid p cJAN ae2024048300 v103 a

This study reports the synthesis, characterization, and docking analysis of 21 novel compounds, including asymmetric dihydropyridines (4a-4o) and chalcones (6a-6f), derived from coupling 1,3-(substituted)-diphenyl-1H-pyrazole-4-carbaldehyde with active methylene compounds and 3-acetyl-4-hydroxycoumarin, respectively. Structural confirmation was achieved through 1H and 13C NMR, IR, and mass spectrometry. Biological screening against mycobacterium tuberculosis H37Ra identified compounds 4b, 4d, 4f, 4g , 4i, 4k, 6e, and 6f as significant antitubercular agents. Antibacterial evaluation at 30 mu g/mL showed selective inhibition of gram-positive bacteria, with compound 6e active against Staphylococcus aureus and Bacillus subtilis, and 6f showing activity specifically against S. aureus. Docking studies indicated effective InhA binding (Delta G = -3.52 to -7.27 kcal/mol) and inhibition constants ranging from 2640 to 4.71 mu M. Key binding interactions with residues TYR156 and ILE192 were observed, enhancing affinity, particularly for compound 6e. The SAR analysis emphasized the enhanced antitubercular potency of 2-chloroacetyl and 2,4-dichlorobenzoyl substitutions in the dihydropyridine series, while in the chalcone series, specific substitutions, such as the 3-nitro substitution in 6e, enhance antitubercular and antimicrobial potency due to stronger hydrogen bonding and increased polar surface area, while the 4-fluoro substitution in 6f confers selective activity against S. aureus.

10a110a4-dihydropyridine10a4-hydroxy coumarin10aBiological activity10aIn silco studies10aPyrazole1 aBavishi, Abhay1 aVala, Hardev1 aRadadiya, Ashish1 aSwami, Sagar1 aThakrar, Shailesh1 aSarkar, Dhiman1 aShah, Anamik uhttps://library.ncl.res.in/content/synthesis-biological-screening-and-molecular-docking-hybrid-pyrazole-scaffolds