2. Academic Validation
  3. Evaluation of antibacterial, cytotoxicity, and apoptosis activity of novel chromene-sulfonamide hybrids synthesized under solvent-free conditions and 3D-QSAR modeling studies

Evaluation of antibacterial, cytotoxicity, and apoptosis activity of novel chromene-sulfonamide hybrids synthesized under solvent-free conditions and 3D-QSAR modeling studies

  • Sci Rep. 2024 Jun 5;14(1):12878. doi: 10.1038/s41598-024-63535-5.
Shakila Ghomashi 1,  Reihane Ghomashi 2,  Mohammad Sadegh Damavandi 3 4,  Zeynab Fakhar 5,  Seyedeh Yasaman Mousavi 6,  Azhar Salari-Jazi 7 8,  Sajjad Gharaghani 9,  Ahmad Reza Massah 10 11
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Shahreza Branch, Islamic Azad University, P.O. Box 311-86145, Shahreza, Isfahan, Iran.
  • 2 Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
  • 3 Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 4 Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 5 Laboratory of Bioinformatics and Drug Design (LBD), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
  • 6 Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
  • 7 Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. azhar_sallari@yahoo.com.
  • 8 Department of Drug Development and Innovation, Behban Pharmed Lotus, Tehran, Iran. azhar_sallari@yahoo.com.
  • 9 Laboratory of Bioinformatics and Drug Design (LBD), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. s.gharaghani@ut.ac.ir.
  • 10 Department of Chemistry, Shahreza Branch, Islamic Azad University, P.O. Box 311-86145, Shahreza, Isfahan, Iran. massah@iaush.ac.ir.
  • 11 Department of Chemistry, Brock University, St. Catharines, ON, Canada. massah@iaush.ac.ir.
PMID: 38834651 DOI: 10.1038/s41598-024-63535-5
Abstract

In this study, eleven novel chromene sulfonamide hybrids were synthesized by a convenient method in accordance with green chemistry. At first, chromene derivatives (1-9a) were prepared through the multi-component reaction between aryl aldehydes, malononitrile, and 3-aminophenol. Then, synthesized chromenes were reacted with appropriate sulfonyl chlorides by grinding method to give the corresponding chromene sulfonamide hybrids (1-11b). Synthesized hybrids were obtained in good to high yield and characterized by IR, 1HNMR, 13CNMR, CHN and melting point techniques. In addition, the broth microdilution assay was used to determine the minimal inhibitory concentration of newly synthesized chromene-sulfonamide hybrids. The MTT test was used to determine the cytotoxicity and apoptotic activity of the newly synthesized compounds against fibroblast L929 cells. The 3D‑QSAR analysis confirmed the experimental assays, demonstrating that our predictive model is useful for developing new Antibacterial inhibitors. Consequently, molecular docking studies were performed to validate the findings of the 3D-QSAR analysis, confirming the potential binding interactions of the synthesized chromene-sulfonamide hybrids with the target Enzymes. Molecular docking studies were employed to support the 3D-QSAR predictions, providing insights into the binding interactions between the newly synthesized chromene-sulfonamide hybrids and their target Bacterial enzymes, thereby reinforcing the potential efficacy of these compounds as Antibacterial agents. Also, some of the experimental outcomes supported or conflicted with the pharmacokinetic prediction (especially about compound carcinogenicity). The performance of ADMET predictor results was assessed. The work presented here proposes a computationally driven strategy for designing and discovering a new sulfonamide scaffold for Bacterial inhibition.

Keywords

3D-QSAR modeling studies; ADMET; Antibacterial; Apoptosis activity; Chromenes; Cytotoxicity activity; Docking; Pharmacokinetics; Solvent-free conditions; Sulfonamides; Synthesis.

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