In the present investigation, some novel nitro Mannich bases derived from Michael type addition of activated nitro olefin, β‐nitrostyrene with various amines either primary or secondary including some amino sugars were designed and synthesized. The produced Mannich bases have been full characterized through different spectroscopic techniques. Antimicrobial evaluation has been performed against the Gram positive S. aureus and methicillin‐resistant S. aurues (MRSA) infections. 5 of the synthesized compounds represent the best candidates in the biological screening, they have exhibited good activity with MIC values range from 100 to 250 μg/ml. The active agents have been tested for pyruvate kinase inhibition activity with % of inhibition range from 30 to 79 % with IC50 in a nano molar range. They also exhibited significant Pyruvate kinase inhibition in nanomolar range with IC50 of 1066, 662, 1887, 418 and 1128 ng/ml, respectively (versus 196 ng/ml for AZD7545). Molecular docking calculations for active agents were performed. A complete conformational analysis molecular modeling utilizing Gaussian 09 program (HF/DFT) was used to verify the mode of bonding through the optimized geometries as well as essential quantum parameters were calculated using frontier energies (EHOMO & ELUMO) for the active candidates indicating the overall stability of the structure.
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Synthesis, biological evaluation, and molecular docking of pyrazoline-linked benzenesulfonamides and diaryl 1,5-benzothiazepines prepared from new chalcones are described and elucidated. Novel compounds were studied for their in vitro anticancer profiles on HepG2, HEK-293, MCF-7, and MDA-MB-231 cancer cell lines, where, compounds IIb, III, and IVe demonstrated high to moderate cell proliferation inhibition activity. Compound IIb was further assessed for tubulin polymerization inhibition effects due to its high potency, which showed superior suppression compared to the reference drug. It induced cell cycle cessation at the G2/M phase and accumulation of cells in the pre-G1 phase, preventing its mitotic cycle. In addition, compound IIb activated caspase-7, mediating apoptosis of HepG2 cells. These findings, along with molecular docking and pharmacophore constructed models, provide a new scaffold of cytotoxic agents targeting tubulin.
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