Spectral bio-markers, hirshfeld analysis, molecular docking and cytotoxicity of bronchodilatic drug 1,3-dimethylxanthine: A vibrational approach

Abstract

The drug action of Bronchodilatic Drug 1,3-dimethylxanthine (THP) are mediated by the inhibition of phosphodiesterase (PDE) and increase of intracellular cyclic adenosine monophosphate (cAMP) which mediates smooth muscular mediations. The vibrational spectral investigations of THP and the bio-markers of methylxanthine bronchodilators along with DFT computations explains the structural and bonding features, charge-transfer interactions, nature of hydrogen bonding etc. The strong and simultaneous occurrence of 8a mode in IR and Raman spectra reveals the involvement of benzene ring in the intermolecular charge transfer interaction through NH⋯O hydrogen bonding. The spectral bio-marker bands of methylxanthine based bronchodilatic drugs, corresponding to ring CC stretching ca 1599 cm−1 (8a mode) and CO stretching vibrations ca 1650 cm−1 stretching vibrations are found to be strongly and simultaneously active in both IR and Raman spectra as observed in other bronchodilators viz, caffeine and theobromine. It is observed that the THP molecule possesses reasonably high dipole moment results in moderate βtotal value which favours charge transfer interactions that help in binding with the receptor phosphodiesterase enzyme. THP in the binding pocket is stabilized through the attractive non-covalent T-shaped π-π interaction, π-cation interactions and π-alkyl interactions between the aromatic rings of THP with the amino acid residues suggest that through these interactions the ligand THP binds with albumin protein that inhibits the synthesis of phosphodiesterase enzyme and other mediators in the process of improving its anti-asthmatic activity.