In continuation of our previous work, novel sulphonamide–thiazole hybrids were synthesized and evaluated for anticancer activity against NCI–H226 lung carcinoma cells, with WI-38 fibroblasts as a normal control. Among the tested compounds, fluoro-substituted compound 14 exhibited the highest potency (IC₅₀ = 16.10 μg/mL) and selectivity (SI = 183.79), while halogen- and nitro-substituted analogs (4–6) showed moderate activity. Quantum mechanical studies using DFT (B3LYP/6-311G(d,p), SMD solvent) rationalized the observed SAR, highlighting the role of electronic and steric effects in modulating activity. Molecular docking revealed stronger binding of compound 14 to EGFR (−8.2 kcal/mol) than TP53 (−7.1 kcal/mol), suggesting EGFR as its primary target, with TP53 interactions supporting apoptotic signalling. ADMET predictions indicated favourable drug-likeness, low toxicity, and non-mutagenicity. Molecular dynamics simulations over 100 ns confirmed that compound 14 forms highly stable complexes with both EGFR and TP53, preserving secondary structures, and consistent hydrogen-bonding and hydrophobic interactions, with MM-GBSA free energies of ~ –75 kcal mol⁻¹. Free energy landscape and principal component analyses demonstrated conformational adaptability and long-term stability. Collectively, these results identify compound 14 as a potent, selective, and energetically favourable dual-target anticancer agent, providing a strong mechanistic foundation for further preclinical development.

Background

Indolinone and spiro-indoline derivatives have been employed in the preparation of different important therapeutic compounds required for treatment of anticonvulsants, antibacterial, Antitubercular, and anticancer activities. Schiff bases have been found to possess various pharmacological activities such as antitubercular, plant growth inhibiting, insecticsidal, central nerve system depressant, antibacterial, anticancer, anti-inflammatory, and antimicrobial. Mannich bases have a variety of biological activities such as antibacterial and antifungal activities.

Results

In this study, a green, rapid and efficient protocol for the synthesis of a new series of Schiff bases from spiro[indoline-3,4′-pyran]-3′-carbonitrile derivatives using ammonium chloride as a very inexpensive and readily available reagent. The prepared compounds were assessed in vitro for their antimicrobial activity. Also, the cytotoxic activity of the prepared compounds was assessed in vitro against human cells line MCF7 breast cancer.

Conclusion

Good activity was distinguished for Schiff bases from spiro[indoline-3,4′-pyran]-3′-carbonitriles, with some members recorded higher antimicrobial and anti-breast cancer activities.

A simple and convenient 1,3-dipolar cycloaddition of non-stabilised azomethine ylides derived from isatins and L-proline, in a variety of different solvents, to (Z)-4-arylidene-1-phenylpyrazolidine-3,5-diones as dipolarophiles afforded a series of novel dispiro[pyrazolidine-4,3′-pyrrolizidine-2′,3″-indoline]-2″,3,5-triones regioselectively and in good yields.

A facile one-pot synthesis of spirooxindolinopyrrolizidines incorporating the pyrene moiety was accomplished in good yields through a 1,3-dipolar cycloaddition reaction of 3-aryl-1-(pyren-1-yl)prop-2-en-1-one derivatives with in situ-generated azomethine ylides.

A simple and highly efficient protocol was developed for one-pot synthesis of polyfunctionalized spirothiazolidin-4-ones using sulfonated mesoporous silica (MCM-SO₃H) as a heterogenous and reusable acidic catalyst. In comparison to the reported synthetic methods for the synthesis of thiazolidin-4-one and spirothiazolidin-4-one derivatives, this strategy provides superior yields under mild conditions, while avoiding hazardous solvents.

The regio- and stereochemical polar [3 + 2] cycloaddition of azomethine ylides, which were generated in situ by the reaction of isatin and sarcosine or benzylamine, with (E)-3-aryl-1-(pyren-1-yl)prop-2-en-1-ones as dipolarophiles, was studied using experimental and theoretical methods. The chemical structures and relative configurations of all products have been fully established by 1D and 2D homonuclear and heteronuclear correlation NMR spectrometry. The effects of the electronic and steric factors of the reactions were discussed. The photophysical properties of the synthesized spiro[indoline-3,2′-pyrrolidin]-2-ones and 5′-phenyl-spiro[indoline-3,2′-pyrrolidin]-2-ones were studied. The mechanism of the reactions was investigated using global and local reactivity indices and frontier molecular orbital (FMO) analysis at the B3LYP/6-31G level of theory. The relationship between the electrophilicity index ω of the dipolarophiles and the Hammett constant σ_p has been studied. The theoretical scale of reactivity correctly explains the electrophilic activation/deactivation effects promoted by electron-withdrawing and electron-releasing substituents in the para-position of the dipolarophiles.

A simple, convenient, and regioselective 1,3-dipolar cycloaddition of 9-diazo-9H-fluorene or diphenyldiazomethane to 2-arylidene-1H-indene-1,3(2H)-diones afforded a series of novel dispiro[indane-2,3′-pyrazole-5′,9″-fluorene] and spiro[indene-2,3′-pyrazole] derivatives in moderate to excellent yields. Chemical structures of all products have been fully established by 1D (¹H, ¹³C, ¹³C-DEPT 90) and 2D homonuclear and heteronuclear correlation NMR spectrometry experiments (¹H-¹H-DQF-COSY, ¹H-¹H-TOCSY, ¹³C-¹H-HSQC, ¹³C-¹H-HMBC, ¹H-¹H ROESY, and HSQC-TOCSY) and regioselectivity of the reported procedure has been demonstrated in all products. DFT reactivity indices of these cycloaddition reactions have been studied. 1,3-Dipolar cycloaddition of 9-diazo-9H-fluorene and diphenyldiazomethane to 2-arylidene-1H-indene-1,3(2H)-diones as dipolarophiles are reactions governed by a concerted mechanism exhibiting high regioselectivity.

Limestone mining waste and its derived CaO were checked as an adsorbents of pb²⁺, Cu²⁺, and Cd²⁺ ions from water solution. The characterization of Limestone and calcined limestone was studied by using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), Scanning Electron Microscope (SEM), and Surface area measurements (BET). The optimum conditions of sorbent dosage, pH, initial concentration, and contact time factors were investigated for pristine limestone and calcined limestone absorbents. The results indicate that the optimum initial concentrations of (C_i) were 1200, 500, and 300 ppm for Pb, Cu, and Cd, respectively, using calcined limestone adsorbent, while using the pristine limestone adsorbent, the corresponding optimum initial concentrations were 700, 110, and 50 ppm. In the ternary system sorption, the results indicated that the selectivity …

A novel compound, 2,6-bis-[1-(2-phenylhydrazono)ethyl]pyridine (BPEP), was synthesized and confirmed by NMR and IR spectroscopy. BPEP was examined as an inhibitor for the corrosion of zinc electrode in 1.0 M HCl. The inhibition efficiency of BPEP was assessed through various techniques such as hydrogen evolution, galvanostatic polarization, potentiodynamic anodic polarization, and electrochemical impedance spectroscopy. The inhibiting action of BPEP was explained in terms of the formation of a stable complex between zinc ions and BPEP and then adsorbed onto the zinc surface. The formation of the complex was established by FT-IR spectroscopy. A conductometric titration indicated that the stoichiometry of Zn⁺²:BPEP (metal:ligand) is 1:1. The adsorption follows the Langmuir isotherm. The Galvanostatic polarization measurements have shown that the BPEP molecule acts as a mixed-type inhibitor. The pitting potential shifted in the noble direction, indicating that the inhibition of pitting corrosion of zinc in the presence of BPEP.The activation energy and themodyanamic parameters of the adsorption process were calculated and have been explained.

Six new highly fluorescent 5-(aryl)-1-phenyl-3-(pyren-1yl)-2-pyrazolines were synthesized by reaction of various (E)-3-aryl-1-(pyren-1-yl)prop-2-en-1-ones with phenyl hydrazine in the presence of sulfonated mesoporous silica (MCM-SO₃H) as efficient and eco-friendly acidic catalyst. The chemical structures of all synthesized compounds were illustrated on the basis of spectral data (IR, ¹H NMR and ¹³C NMR). This was followed by photophysical properties-based absorption and emission studies of the target compounds in solutions of different solvent polarities. The microenvironment-sensitive fluorescent pyrazolines labeled with pyrene exhibited valuable fluorescence properties with emission in the range of 600–700 nm with a marked response to change in the environmental polarities. A significant and pronounced red shift was observed in the emission spectrum of 5-(aryl)-1-phenyl-3-(pyren-1yl)-2-pyrazolines Δλ ∼ 50 nm compared to the absorption spectrum Δλ ∼ 10 nm upon increasing the solvent polarity. This indicated the presence of higher dipole moment in the excited state than in the ground state and the transition involved are π-π* transition through the charge transfer phenomena. The fundamental understanding of solvatochromic properties were analyzed through Lippert-Mataga and Reichardts correlations in order to estimate the change in dipole moments (Δμ) which suggested the emissive state of designed fluorescent 2-pyrazoline derivatives is of strong ICT character.