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

• Published in: ChemistrySelect (Weinheim) Vol. 7; no. 28
• Main Authors: Amira, Aϊcha, K'tir, Hacène, Aouf, Zineb, Khaldi, Taha, Bentoumi, Houria, Khattabi, Latifa, Zerrouki, Rachida, Ibrahim‐Ouali, Malika, Aouf, Nour‐Eddine
• Format: Journal Article
• Language: English
• Published: Wiley 27.07.2022
• Subjects: Anti-inflammatory Activity; Bisphosphonate; Chemical Sciences; DFT study; Microwave-assisted synthesis; Molecular Docking; Bisphosphonate; DFT study; Molecular Docking; Microwave-assisted synthesis; Anti-inflammatory Activity
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202201889

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 1H, 13C, 31P 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. Novel sulfamide‐containing bisphosphonates derivatives were synthesized through multicomponent reactions using microwave activation under solvent‐ and catalyst‐ free conditions. The anti‐inflammatory activity and the theoretical calculations of four compounds were determined, and the binding mode between MMP‐8 protein and the ligands was predicted by molecular docking. The results revealed that our lead compounds may be used as a proposed drug for medical applications.