Enhancement of catalytic activity using CoFeLDH for the formation of biologically active diaryl sulfide and propargylamine derivatives: molecular docking, DFT, dynamics, and ADMET analyses of their biocidal and anti-diabetic activities

Abstract

Synthetic clays known as layered double hydroxides (LDHs) have gained attention owing to their diverse range of applications in various fields. LDHs consist of cationic layers that contain anions in the hydrated interlayer to balance the charge. Our synthetic approach has shown that CoFeLDH is a promising reusable catalyst for C–S cross-coupling and A3 coupling reactions. The synthesized compounds were investigated for antimicrobial activities against two Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) and two Gram-negative bacteria (Escherichia coli and Klebsiella pneumonia), and we obtained ethical results. To better understand the observed activities, molecular docking studies were performed to explore new anti-diabetic compounds with different molecular structures. Density functional theory (DFT) was also used to investigate the chemical reactivity and kinetic stability of the compounds 3a–h and 4a–e. The observed binding energies for all molecules were between −6.0 and −8.3 kcal mol⁻¹, indicating strong interactions. We conducted DPPH assays for in vitro antioxidant measurements: sample 1 (compound 4a, 340.98 ± 16.31 µg mL⁻¹) showed a more potent radical scavenging activity than sample 3 (compound 3g, 122.10 ± 7.15 µg mL⁻¹) and ascorbic acid (90.01 ± 3.62 µg mL⁻¹). The α-amylase inhibitory assays were also carried out for the compounds 3g and 4a. Both sample 1 (compound 4a, 54.89 ± 5.05 µg mL⁻¹) and sample 3 (compound 3g, 58.95 ± 4.581 µg mL⁻¹) showed significant (p < 0.05) α-amylase inhibitory activity as compared to acarbose (143.62 ± 16.31 µg mL⁻¹), an antidiabetic drug. Further, we carried out an in vivo antidiabetic assay in rats for compound 4a. The α-amylase inhibition activity of compound 4a (SR) showed an IC₅₀ value of 112.98 µg mL⁻¹, while standard acarbose showed an IC₅₀ value of 63.76 µg mL⁻¹. Similarly, the α-glucosidase inhibition activity revealed that the SR showed an IC₅₀ value of 111.42 µg mL⁻¹, while the standard acarbose showed an IC₅₀ value of 78.53 µg mL⁻¹, which signifies a reduced diabetic risk in rats.