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

Meriem Guerfi; Malika Berredjem; Ali Dekir; Rania Bahadi; Seif-Eddine Djouad; Tan Ouk Sothea; Rayenne Redjemia; Billel Belhani; Meriem Boussaker

doi:10.1007/s11030-023-10630-w

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

Mol Divers. 2023 Apr 3. doi: 10.1007/s11030-023-10630-w. Online ahead of print.

Authors

Meriem Guerfi¹, Malika Berredjem², Ali Dekir¹, Rania Bahadi¹, Seif-Eddine Djouad^{1

3}, Tan Ouk Sothea⁴, Rayenne Redjemia¹, Billel Belhani¹, Meriem Boussaker¹

Affiliations

¹ Chemistry Department, Laboratory of Applied Organic Chemistry, Synthesis of Biomolecules and Molecular Modelling Group, Sciences Faculty, Badji-Mokhtar Annaba University, Box 12, 23000, Annaba, Algeria.
² Chemistry Department, Laboratory of Applied Organic Chemistry, Synthesis of Biomolecules and Molecular Modelling Group, Sciences Faculty, Badji-Mokhtar Annaba University, Box 12, 23000, Annaba, Algeria. mberredjem@yahoo.fr.
³ Laboratory of Therapeutic Chemistry of Hospitalo-University Center Benflis Touhami, Batna, Algeria.
⁴ Laboratoire Peirene, EA7500 Université de Limoges, 123 Avenue Albert Thomas, 87000, Limoges Cedex, France.

PMID: 37010709
DOI: 10.1007/s11030-023-10630-w

Abstract

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.

Keywords: ADME analysis; Anticancer activity; DFT study; Glutamate carboxypeptidase II inhibition; Molecular docking; α-sulfamidophosphonates.