Synthesis, structural characterization, computational studies, and in silico and in vitro biological activities of cyclodextrin inclusion complex with sulfonamide derived from L-valine as antimicrobial and anti-HIV-1 agents

An inclusion complex of sulfonamide derived from L-valine (dimethyl 2, 2′- (sulfonylbis (azanediyl)) bis (3-methylbutanoate), (DSBM), with cyclodextrin has been synthesized and characterized using different spectroscopic techniques: FT-IR, ¹H NMR, ¹³C NMR, 2D NMR, and UV–Visible. The DFT/B3LYP method was utilized to perform theoretical calculations in order to examine vibrational properties, determine NBO (natural bond orbital) energies, and clarify the frontier molecular orbitals (FMOs). Time-dependent density functional theory TD-DFT calculations were realized for the optimized DSBM and its complex structures. To elucidate the different intermolecular interactions in the complex, a detailed analysis of the topological charge density based on the quantum theory of atoms in molecules (QTAIM) was performed. Moreover, the DHPS from Staphylococcus aureus (PDB code: 1AD4), HIV-1 reverse transcriptase (PDB code: 4KV8), and HIV-1 protease (PDB code: 4Q5M) were selected for molecular docking study. The in silico results indicate that the DSBM and β-CD inclusion complex can be used as a better inhibitor of DHPS enzyme from Staphylococcus aureus bacteria strain. The interaction between DSBM-β-CD inclusion complex and HIV-1 reverse transcriptase (RT) exhibits a higher binding energy (− 147.80 kcal/mol) than that of the drug reference nevirapine (− 103.43 kcal/mol) and DSBM (− 85.53 kcal/mol). The in silico evaluation against HIV-1 protease reveal that the inclusion complex presents antiviral properties better than the free ligand DSBM. Therefore, the in vitro antioxidant activity was evaluated using DPPH radical scavenging. The data show that the cyclodextrin inclusion complex displays an antioxidant activity better than the DSBM and ascorbic acid with inhibition concentration values of 472.71, 427.59, and 513.01 µg/mL for DSBM-β-CD complex, DSBM, and ascorbic acid, respectively. These values reveal that the complexation with β-CD enhances the antioxidant properties. The antimicrobial activity was realized against Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 4157), and Bacillus subtilis (ATCC 9372) bacteria strains; Candida albicans (ATCC 24433) yeast strain; and Aspergillus niger (ATCC 16888) mold strain. The results show that the synthesized compounds are more active against Aspergillus niger with an inhibition zone diameter of 90 mm for both DSBM and its β-CD complex. These results indicate that the formed compounds can act as potent antifungal agents.