TPGS-mediated one-pot synthesis, XRD structural analysis, antimicrobial evaluation and molecular docking of novel heterocycles as potential inhibitors of p53-MDM2 protein

• Published in: Journal of molecular structure 2020-02, Vol.1202, p.127252, Article 127252
• Main Authors: Anand, K., Naicker, Tricia, Baijnath, Sooraj, Mphahlele, Malose J., Katari, Naresh Kumar, Zamisa, Sizwe J., Balakumar, C., Vijayakumar, K., Palanisamy, Subramanian, Saravanan, Muthupandian, Boomi, P., Chuturgoon, Anil
• Format: Article
• Language: English
• Subjects: Molecular docking; One-pot synthesis; p53-MDM2 protein; TPGS; XRD
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2019.127252

Novel heterocyclic bioactive small molecules bearing thioether moiety, fluorine containing dihydro pyridine and dihydro pyran were synthesized and characterized using spectroscopic methods (FT-IR, 1H, 13C and 19F NMR), LC-MS and SC-XRD. The reaction conducted is highly environment-friendly involving d-α-Tocopherol polyethylene glycol succinate (TPGS) - Water binary solvent as reaction medium. All of the synthesized final compounds were evaluated against 2 g-negative [Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853)] and 1 g-positive [Staphylococcus aureus (ATCC 29213)] bacterial strains by in vitro. Molecular docking experiments were carried out against p53-MDM2 tumor suppressor protein to gain more insights into the binding mode of the final compounds. In this study, we discovered potent p53-MDM2 inhibition by 2-thiobenzyl-3-formyl quinoline, 2-thio-1,2-dihydroquinoline-3-formyl N-substituted thiosemi-carbazone and fluorine substituted new pyridine and pyran derivatives by structure-based design. [Display omitted] •TPGS surfactant allows one-pot synthesis, excellent yields in shorter time.•TPGS surfactant highly reactive in water medium.•Synthesized compounds characterized by FT-IR, NMR, SXRD, MS.•Compounds showed favourable interactions with p53-MDM2 protein.