Design, Synthesis, and Spectroscopic Studies of Some New α-Aminophosphonate Analogues Derived from 4-Hydroxybenzaldehyde with Special Reference to Anticancer Activity

Abstract

Omar M Ali,1 Mohammed T Alotaibi,1 Yasser H Zaki,2 Hamada H Amer3 1Department of Chemistry, University College of Turabah, Taif University, Taif, 21944, Saudi Arabia; 2Department of Chemistry, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt; 3Department of Animal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, EgyptCorrespondence: Yasser H Zaki; Omar M Ali, Email [email protected]; [email protected]: As biological activity components, α-aminophosphonates and their moieties play important roles in medicinal chemistry. Alpha-phosphonic acids are significant α-amino acid counterparts. Due to its strong biological activity, this class of molecule has recently been discovered to have numerous medical applications.Results and Discussion: A new class of α-aminophosphonates and arylidene derivatives was synthesized. Various spectroscopic and elemental analyses were used to confirm the prepared products. The produced materials were tested as anticancer against breast carcinoma cells and normal human cells (PBMC). Besides the analysis results, it was found that ( 7b, 4c, 5k, 6, 5a, 7c, 5f, 5b, and 5g) against MCF-7 line cells. As a reference anticancer drug, 5-fluorouracil was used. The anticancer activities showed that the compounds 7b, 4c, containing α-aminophosphonate and Schiff base groups, respectively, showed high inhibition activity against the MCF-7 cell line, with 94.32% and 92.45% inhibition compared to the inhibition by 5-FU with 96.02% inhibition. The results showed that the compounds 5k, 7b, 6, and 5a, respectively, had very low activity against normal human cells PBMC, with 12.77%, 13%, 13.13%, and 17.88% inhibition compared to the inhibition by 5-FU with 12.50% inhibition. The binding energy for non-bonding interactions between the ligand (studied compounds) and receptor, thymidylate synthase, was determined using molecular docking (pdb code: 1AN5).Conclusion: α-aminophosphonate derivatives, arylidines, and disphosphonate derivatives derived from 4-hydroxybenzaldehyde were synthesized, purified, elucidated by spectroscopic analysis, and finally tested against carcinoma breast cancer to give high to moderate to low activity.Graphical Abstract: Keywords: synthesis, phosphonates, arylidene derivatives, 4-hydroxybenzaldehyde, anticancer activity

Keywords

• synthesis
• phosphonates
• arylidene derivatives
• 4-hydroxybenzaldehyde
• anticancer activity