Synthesis, characterization, antimicrobial and interaction studies of pteridines with human serum albumin: A combined multi-spectroscopic and computational study

• Published in: Journal of molecular structure 2022-02, Vol.1250, p.131857, Article 131857
• Main Authors: Raghu, M.S., Kumar, K. Yogesh, Veena, K., Kumar, C.B. Pradeep, Almalki, Amani Salem, Mani, G., Alasmary, Fatmah Ali, Prashanth, M.K.
• Format: Article
• Language: English
• Subjects: Antimicrobial; HSA; Molecular docking; Pteridine; Spectroscopy
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.131857

•Novel pteridine derivatives was synthesized and characterized.•Compound 3b and 3e is most potent antimicrobial member.•Binding properties and parameters of test compounds to HAS established based on the multi-spectroscopic techniques.•Molecular docking studies showed that the compounds have strong binding affinity towards HSA.•Computational studies of test compounds with HSA substantiate the experimental findings. A novel series of pteridine derivatives (3a–e) was synthesized, and the structures of these molecules were established using elemental analysis and numerous spectroscopic methods. The disk diffusion technique was used to examine the antimicrobial potential of the newly synthesized molecules. Among the compounds examined, the 3b and 3e compounds would have the highest impact against the examined bacterial and fungal strains. The compounds minimum inhibitory concentration (MIC) was observed to be in the line of 0.41–6.83 μM. UV-vis absorption, fluorescence quenching, FT-IR spectroscopy and circular dichroism (CD) along with molecular docking methods, were studies to assess the binding behavior of efficient pteridine derivatives (3b and 3e) with human serum albumin (HSA). Formation of HSA-test compounds complex indicates the static quenching phenomena during fluorescence quenching of HSA by test compounds. Synthesized 3b and 3e were further evaluated for three basic binding sites of HSA including subdomains IIA, IIIA, and IB, using molecular docking studies. Hydrophobic and interaction through hydrogen bonding influenced the binding pathway of HSA with test molecules, according to the molecular docking data. Furthermore, the DFT technique was used to optimize the molecular geometry of potent 3b and 3e compounds using the B3LYP hybrid functional and the 6–311 + G(d, p) basis set. The optimized structure closely aligns with the test findings. The electrostatic potential framework was produced to visualize the molecule's energy distribution and chemical reactive areas. [Display omitted]