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

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 H-1, C-13, P-31 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.