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Abstract: A detailed spectroscopic analyses of a newly synthesized ethyl 2-cyano-3-[5-(hydrazinooxalyl–hydrazonomethyl)-1H-pyrrol-2-yl]-acrylate (3) have been carried out using 1H and 13C NMR, UV–Visible, FT-IR and mass spectroscopic techniques. All the quantum chemical calculations have been carried out using DFT level of theory, B3LYP functional and 6-31G(d,p) as basis set. The 1H and 13C NMR chemical shifts are calculated using gauge including atomic orbitals (GIAOs) approach in DMSO-d 6. TD-DFT is used to calculate the energy (E), oscillatory strength (f) and wavelength absorption maxima (λ max) of various electronic transitions and their nature within molecule. Natural bond orbital (NBO) analysis is carried out to investigate the various intra and intermolecular interactions in dimer and their corresponding second order stabilization energy (E (2)). A combined theoretical and experimental vibrational analysis confirms the existence of dimer and the binding energy of dimer is calculated as 9.21kcal/mol using DFT calculations. To determine the energy and nature of different interactions topological parameters at bond critical points (BCPs) have been analyzed by Bader’s ‘atoms in molecules’ (AIMs) theory in detail. Electrophilic charge transfer (ECT) is calculated to investigate the relative electrophilic or nucleophilic behavior of reactant molecules involved in chemical reaction. Global electrophilicity index (ω =5.5836eV) shows that title molecule (3) is a strong electrophile. The local reactivity descriptors such as Fukui functions , local softness and electrophilicity indices analyses are performed to determine the reactive sites within molecule. [Copyright &y& Elsevier]

• A series of new hydrazones were synthesized with good yield. • Synthesized compounds were evaluated for antibacterial, anti-inflammatory, and anti-oxidant activities. • Upon comparing the synthesized molecules with the commonly prescribed medication Diclofenac sodium, we observed a significant enhancement in anti-inflammatory efficacy. • The synthesized compounds demonstrated a notable inclination for DPPH scavenging in the antioxidant assessment, further highlighting their potential in combating oxidative stress. • In silico molecular docking and dynamic investigations were performed to better understand the binding mechanism of the synthesized hydrazones with the target. Hydrazones, which are azomethine-containing active chemicals with a N(H)N CH group, are extensively researched due to their versatility in pharmacology and ease of synthesis. The synthesized hydrazone compounds were examined by FTIR, UV–visible, EI-MS, 1H NMR, and 13C NMR spectroscopy, and they possessed azomethine linkages. Using the disc diffusion process and minimum inhibitory concentration (MIC) techniques, the compounds were tested for their antibacterial activity. By using the denaturation of bovine serum albumin technique to the synthesized compounds, their anti-inflammatory properties were further examined. Comparing the synthesized molecules to the common medication diclofenac sodium, considerable anti-inflammatory efficacy was observed. Synthesized compounds' antioxidant results revealed a remarkable tendency for DPPH scavenging. Further in silico molecular docking and dynamic studies were evaluated to understand the binding mechanism of the synthesized hydrazones with the target. [Display omitted] [ABSTRACT FROM AUTHOR]

• Novel coumarin-thioether conjugates were synthesised and characterised. • The synthesised compounds are assessed for in vitro anti-TB activity (H 37 Rv strain). • Compound 6b (MIC = 0.39 µg/mL) was twofold more active than Rifampin (0.8 µg/mL). • Compounds 6b and 6f possessed low level of cytotoxicity against Vero cells. • Molecular docking study revealed higher C-score values that supports the findings. In this work, we report a series of 4-(2,6-dimethylphenyl)thio)methyl)-2H-chromen-2-one conjugates as promising leads to treat tuberculosis. Spectroscopic and other analytical methods were used to validate the synthesised compounds. The compounds were assessed for in vitro anti-tubercular activity with the H 37 Rv strain of Mycobacterium tuberculosis. Further, cytotoxicity studies were performed using Vero cells. Most of the synthesised conjugates were effective and displayed notable activity with MIC values in the range 0.39–12.5 µg/mL.The most diligent compound 6b (MIC = 0.39 µg/mL) was twofold more active than standard anti-TB drug Rifampin (0.8 µg/mL) and was comparable to Isoniazid (0.1 µg/mL). Compound 6f also displayed exemplary activity (MIC 0.78 µg/mL). Both compounds 6b and 6f possessed low levels of cytotoxicity, Molecular docking evaluation of the synthesised conjugates and 4DQU ligand demonstrated that the synthesised conjugates had higher C-score values that further supports the obtained results. It indicates compound 6b and 6f are promising lead compounds in search of novel antitubercular drug-like molecules. [Display omitted] [ABSTRACT FROM AUTHOR]

• Anticancer and anti-TB activity of novel coumarin-azaspiro conjugates (1a-1l). • 1f exhibited the most potent activity against MDA-MB-231cell line (IC 50 = 9.05 µM). • 1g showed most potent activity against A549 cell line (IC 50 = 7.05 µM). • 1c is found to be the hit candidate against MTBH 37 Rv strain with MIC 0.78 µg/mL. In this work, a series of new 8-[(substituted 2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione derivatives (1a - 1l) is synthesized and characterized by 1H NMR, 13C NMR, FT-IR, GC-MS and elemental analysis. In addition, the structure of compound 1k has been elucidated using single crystal X-ray diffraction techniques. The synthesized compounds are screened for their anticancer and anti-TB activity. Preliminary anticancer results showed that compounds (1a - 1l) exhibit moderate to potent activity against MDA-MB-231, A549, HT-29 and Hela cancer cell lines. Compound 1f exhibited the most potent activity against MDA-MB-231cell line with IC 50 value of 9.05 µM concentration, compound 1g and 1h showed potent activity against A549 cell line with IC 50 value of 7.05 and 13.31 µM concentration respectively. Compound 1j showed good cytotoxicity against Hela cell line with IC 50 of 16.14 µM, whereas, compound 1l is found to be moderately active against HT-29 cell line with IC 50 of 18.07 µM. Anti-tubercular activity revealed that compound 1c, 1d, 1g, 1h and 1j have significant activity against MTBH 37 Rv strain with MIC 0.78, 1.56, 0.19, 0.39 and 0.78 µg/mL respectively. Further, to investigate the mechanism of anti-TB activity and detailed intermolecular interactions between the synthesized compounds, molecular docking studies are performed. [ABSTRACT FROM AUTHOR]