One‐Pot Microwave‐Assisted Synthesis, in Vitro Anti‐inflammatory Evaluation and Computer‐Aided Molecular Design of Novel Sulfamide‐Containing Bisphosphonates Derivatives

Aϊcha Amira (1) , Hacène K'Tir (1) , Zineb Aouf (1) , Taha Khaldi (2) , Houria Bentoumi (1) , Latifa Khattabi (3) , Rachida Zerrouki (4) , Malika Ibrahim-Ouali (5) , Nour‐eddine Aouf (1)

1 UBMA - Université Badji Mokhtar Annaba
2 CRBt - Centre de Recherche en Biotechnologie
3 CHEMS - Unité de Recherche de Chimie de l'Environnement et Moléculaire Structurale
4 PEIRENE - PEIRENE
5 ISM2 - Institut des Sciences Moléculaires de Marseille

An eco-friendly and one-step microwave-assisted green synthesis of new functionalized bisphosphonates derivatives was described by a three-component reaction of aromatic sulfamide with triethyl orthoformate and diethyl phosphite. The synthesized compounds were characterized by 1 H, 13 C, 31 P NMR and IR analysis. Some of these compounds were tested for in vitro anti-inflammatory activity and showed moderate inhibition compared to diclofenac as standard drug. Furthermore, to rationalize the observed biological data, several in silico approaches have been used to explain Structure-Activity Relationship study (SAR) based on DFT calculation, molecular docking, pharmacodynamic, pharmacokinetic and toxicity profiles of sulfamide-containing bisphosphonates derivatives as anti-inflammatory drugs. The results of the in vitro and in silico activities prove that the compound 4 b have the ideal structural requirements for further development of novel anti-inflammatory agents.

Domains: Chemical Sciences; Medicinal Chemistry

Aϊcha Amira, Hacène K'Tir, Zineb Aouf, Taha Khaldi, Houria Bentoumi, et al.. One‐Pot Microwave‐Assisted Synthesis, in Vitro Anti‐inflammatory Evaluation and Computer‐Aided Molecular Design of Novel Sulfamide‐Containing Bisphosphonates Derivatives. ChemistrySelect, 2022, 7 (28), pp.e202201889. ⟨10.1002/slct.202201889⟩. ⟨hal-03959428⟩