Tuning surface properties of thiophene-based thin films on glass substrates for cancer cell adhesion, drug release control, and computational analysis

Abstract

This study explores the potential of six novel thiophene derivative thin films (THIOs) for reducing cancer cell adhesion and enhancing controlled drug release on inert glass substrates. Thiophene derivatives 3a-c and 5a-c were synthesized and characterized using IR, ¹H NMR, ¹³C NMR, and elemental analysis before being spin-coated onto glass to form thin films. SEM analysis and roughness measurements were used to assess their structural and functional properties. Biological evaluations demonstrated that the films significantly reduced HepG2 liver cancer cell adhesion (~ 78% decrease vs. control) and enabled controlled drug release, validated through the Korsmeyer-Peppas model (R² > 0.99). Theoretical studies, including in-silico target prediction, molecular docking with JAK1 (PDB: 4E4L), and DFT calculations, provided insights into the electronic properties and chemical reactivity of these compounds. Notably, compound 5b exhibited the best binding energy (-7.59 kcal/mol) within the JAK1 pocket, aligning with its observed apoptotic behavior in cell culture. DFT calculations further revealed that 5b had the lowest calculated energy values; -4.89 eV (HOMO) and - 3.22 eV (LUMO), and the energy gap was found to be 1.66 eV, supporting its role in JAK1 inhibition and cancer cell adhesion reduction. These findings underscore the promise of thiophene derivatives in biomedical applications, potentially leading to safer surgical procedures and more effective localized drug delivery systems.

Keywords: Cancer adhesion; DFT; Docking; Drug release; Hepatocellular; Thin film; Thin film glass; Thiophene.

Scheme 1

Synthesis of the novel 3-hydroxy thiophenes 3a–c and 3-methyl thiophenes 5a–c.

Fig. 1

Scan electron microscope images for samples 3a–c, 5a–c (1000× magnification) showing surface morphology of thin films prepared via spin coating.

Fig. 2

Surface plot and surface roughness curves for samples 3a–c and 5a–c.

Fig. 2

Surface plot and surface roughness curves for samples 3a–c and 5a–c.

Fig. 3

Korsmeyer–Peppas drug release model for samples 3a–c, 5a–c: excellent fit with R² values ranging from 0.99 to 1, indicating high correlation between experimental and theoretical data.

Fig. 4

Displays optical micrographs captured using an inverted microscope, showing HepG-2 cancer cells on various substrates: (a) 3a–c and 5a–c, rounded, detached cells are often indicative of dying cells, while those maintaining the typical elongated shape are likely still alive, control cells: (b) morphology and distribution of HepG-2 cells without substrate intervention.

Fig. 5

Boxplot comparison of cell area across the control and treated groups. Cell area (µm²), vs. experimental groups. The control group shows the highest variability and extreme outliers, while all treated groups exhibit reduced spread and fewer outliers, indicating more uniform cell sizes post-treatment.

Fig. 6

Swiss target prediction scanning for compounds 3a–c, 5a–c.

Fig. 7

The interaction between 3-methylthiophene 5b and (PDB ID: 4e4l).

Fig. 8

(a) Optimized structures, (b) electron density, (c) HOMO and LUMO for compound 5b.