Design, synthesis, biological evaluation on immune cell proliferation, crystal structures, spectroscopic characterizations, DFT calculations, ADME analysis, and molecular docking studies with COX of novel tetrazole-Galactopyranosyl analogues

Abstract

• Synthesised a series of novel tetrazole-Galactopyranosyl derivatives. • Good correlations are obtained between the spectra and X-ray data with the predicted ones. • Biological evaluation on immune cell proliferation. • Molecular docking studies with COX of novel tetrazole-Galactopyranosyl derivatives. • The Hirshfeld surface analysis was used to analyze the intermolecular interaction . The new 5-(substituted)-3-(1,2,3,4-di-O-isopropylidene-( D )-galactopyranose) tetrazoles( 1c-8c ) have been achieved by using as starting materials substituted tetrazole ( 1b-8b ) and 1,2,3,4-di- O -isopropylidene-6- O - p -tolylsulfonyl-alpha- D -galactose ( A ) via N-alkylation reactions under phase transfer catalysis (PTC) conditions. All the obtained compounds were characterized by nuclear magnetic resonance spectroscopy. The molecular and crystal structures of two compounds ( 5b and 5c ) were examined by single crystal X-ray crystallography. The Density Functional Theory estimations for compound 5c at the DFT/B3LYP level via 6-31+G(d, p) replicate the structure and geometry. Finally, HOMO and LUMO analysis was used for the charge transfer interface of the structure. Against Cytochrome c Peroxidase (2 × 08), the compounds 3c and 7c interacted with the least binding energy of -9.73kcal/mol and -9.13kcal/mol along with the inhibition constant of 74.23nM and 204.28nM, respectively. All the synthesized compounds showed the excellent anticancer activity and have potential to be used as immunomodulatory agents. The compounds 1c, 3c, 4c, 5c, 6c, 7c and 8c caused an immunostimulatory effect, while compound 2c showed an immuno inhibitory effect.