Anticancer activity, DFT study, ADMET prediction, and molecular docking of novel α-sulfamidophosphonates

A series of novel α-sulfamidophosphonate derivatives (3a-3 g) were synthesized and evaluated for anticancer activity against different human cancer cell lines (PRI, K562, and JURKAT). The antitumor activity of all compounds using the MTT test remains moderate compared to the standard drug chlorambucil. Compounds 3c and 3 g were found to be more active anticancer agent against PRI and K562 cells with IC50 value 0.056-0.097 and 0.182-0.133 mM, respectively. Molecular docking study related to binding affinity and binding mode analysis showed that synthesized compounds had potential to inhibit glutamate carboxypeptidase II (GCPII). Furthermore, computational analysis was performed through Density Functional Theory (DFT) utilizing the B3LYP 6-31 G (d, p) basis set and the theoretical results were correlated with experimental data. The ADME/toxicity analyses carried out by Swiss ADME and OSIRIS software show that all synthesized molecules exhibited good pharmacokinetics, bioavailability, and had no toxicity profile.