The 4-{N-[4-(methanesulfonyl)phenyl]-3-phenylpropa nimidoyl}phenol compound was synthesized according to the method in (V. Koteswara Rao, 13 Oct 2010) ¹⁴ and recrystallized from ethanol (m.p. 190~192 °C, Lit 190 °C).

General method for the synthesis of Schiff bases (compounds SB, Figure 1) is Sulphanilamide (10 gm) was dissolved in 30 ml of ethanol. Substituted aromatic ketone (8ml) in 30 ml ethanol containing Sulphanilamide was added dropwise with stirring and the reaction mixture was continue stirred for 4 hours at room temperature. After the completion of the synthesis, the reaction mixture was cooled in an ice bath. The solid precipitate formed was collected by filtration and thoroughly rinsed with distilled water. To further purify the product, it was recrystallized from ethanol. Evaluation result of various physical characteristics of synthesized compounds is given in result and discussion section.

The FTIR spectrum exhibited characteristic peaks:

1. Screening of the designed derivatives was conducted through ADMET analysis: In Table 3, the synthesized Schiff base derivatives were evaluated based on Lipinski’s Rule of Five (RO5), also known as Pfizer's Rule of Five. This rule specifies that for a compound to be orally active, it should meet certain criteria.

A compound's TPSA should be less than 140 Å2, and the number of rotatable bonds should be less than 10. In Table 4, bioactivity scores were calculated for Schiff base derivatives as GPCR ligands, ion channel modulators (ICM), kinase inhibitors (KI), nuclear receptor ligands (NRL), protease inhibitors (PI), and enzyme inhibitors (EI). A score greater than 0.00 indicates significant activity, scores between 0.00 and -0.5 suggest moderate activity, while scores below -0.5 indicate inactivity.

2. Molecular docking: From the initial screening through Lipinski rule, ADME calculations, and bioactivity score, were successfully passed all the filters and displayed most drug-likeness nature. In Table 6 SBs derivative selected for docking against dihydropteroate synthase enzyme (1AJ2) had exhibited more potent interactions and binding affinity with the target. Binding affinities, and the types of interaction of the docked molecules are examined and the molecules' 2D & 3D docking postures are represented. More the negative docking score show the higher affinity of ligand towards the target.

3. Prediction of Toxicity: In this study, the toxicity of Schiff base (SB) derivatives was evaluated using various toxicological endpoints, including hepatotoxicity, carcinogenicity, mutagenicity, cytotoxicity, and immunogenicity. The toxicity prediction results were presented in a binary format, indicating whether each derivative was classified as active or inactive for each endpoint.

Table 7

Ligand	Hepato-toxicity	Carcino-genicity	Immuno-toxicity	Muta-genicity	Cyto-toxicity
SB	Inactive	Inactive	Inactive	Inactive	Inactive

The synthesis of the novel Schiff base using continuous stirring under solvent-free conditions proved to be an efficient and environmentally friendly method. The physical characterization confirmed the structure and purity of the synthesized Schiff base. The in-silico studies indicated promising biological relevance, showing strong binding affinity to the target protein and favorable ADME properties.

The study titled "Synthesis, Physical Characterization, and In Silico Study of Novel Schiff Base" successfully presented an environmentally friendly method for synthesizing a new Schiff base. The process was followed by detailed physical characterization and computational analysis, demonstrating both practical and theoretical insights into the compound. The synthesis process employed environmentally benign methods, minimizing the use of hazardous reagents and solvents. This approach not only aligns with sustainable chemistry principles but also reduces the environmental impact, making the synthesis process more appealing for industrial and pharmaceutical applications. Physical Characterization include the determination of the melting point provided insights into the purity and thermal stability of the synthesized Schiff base. The solubility profile in various solvents was essential for understanding the compound's interaction with different media, which is crucial for both its practical use and potential biological applications. IR spectral analysis confirmed the presence of the characteristic imine (C=N) group along with other functional groups, validating the successful synthesis of the Schiff base. Computational modeling and in silico analyses provided valuable insights into the Schiff base's molecular geometry, electronic properties, and potential reactivity. These studies complemented the physical characterization, offering a deeper understanding of the compound's behavior at the molecular level and predicting its interactions with biological targets or other chemical entities.

The corresponding author would like to express their sincere gratitude to Dr. Megha T. Salve for their aspiring guidance and also thankful to Neha R. Khilare, Prerana D. Kalyankar for their valuable contributions and support throughout the preparation of this research work.