What does this research mean for the field?

The novel Mannich base derivative PHMT exhibits strong binding interactions with viral enzymes and shows promising nonlinear optical properties, indicating its potential as a biologically active compound for drug discovery. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The research aims to synthesize and evaluate a new Mannich base derivative for potential pharmacological applications.

March 10, 2026

Design, Synthesis, DFT‐Based Characterization, Molecular Docking, and ADMET Evaluation of a Novel Mannich Base Derivative

Key Points

The research aims to synthesize and evaluate a new Mannich base derivative for potential pharmacological applications.
Synthesis of the Mannich base derivative PHMT.
Characterization using IR, H-NMR, and C-NMR spectroscopy.
Density functional theory (DFT) calculations to support experimental findings.
Molecular docking studies to evaluate interactions with specific enzymes.
ADMET evaluation to assess drug-likeness and bioavailability.
PHMT showed strong binding interactions with RdRp and main protease (Mpro) enzymes, with binding energies of -7.80 and -8.50 kcal/mol.
The compound complies with Lipinski's rule of five, indicating good drug-like properties.
PHMT demonstrated promising nonlinear optical properties, along with favorable charge distribution and electrostatic profiles.

Abstract

ABSTRACT In this study, a new Mannich base derivative, 1‐(4‐piperidine carboxamid‐1‐yl‐methyl)‐3‐methyl‐4‐(3‐hydroxy‐4‐methoxybenzylideneamino)‐4,5‐dihydro‐1 H ‐1,2,4‐triazol‐5‐one ( PHMT ), was synthesized and characterized using IR, 1 H‐NMR, and 1 3 C‐NMR spectroscopic techniques. Experimental results were supported by theoretical calculations performed using density functional theory (DFT) with the B3PW91 and B3LYP/6‐311G(d,p) methods. Molecular electrostatic potential (MEP) maps identified the electrophilic and nucleophilic regions of PHMT, while HOMO–LUMO analysis provided insights into its chemical reactivity and stability. Natural bond orbital (NBO) analysis revealed hyperconjugative interactions influencing intramolecular charge transfer and molecular stability, and Mulliken charge distribution identified reactive sites. The calculated dipole moment, polarizability, and first‐order hyperpolarizability values indicate that PHMT possesses promising nonlinear optical (NLO) properties. Molecular docking studies demonstrated strong interactions between PHMT and the 6W75 (RdRp) and 7BV2 (main protease (Mpro/3CLpro)), enzymes, with binding energies of –7.80 and ‐8.50 kcal/mol, respectively. ADMETlab 2.0 analysis showed that PHMT complies with Lipinski's rule of five and exhibits high predicted oral bioavailability. Overall, these findings suggest that PHMT is a biologically active and pharmacologically promising compound with potential applications in drug discovery and development.

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Design, Synthesis, DFT‐Based Characterization, Molecular Docking, and ADMET Evaluation of a Novel Mannich Base Derivative

Key Points

Abstract

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