In vitro and in vivo evaluation of the antimicrobial, antioxidant, cytotoxic, hemolytic activities and in silico POM/DFT/DNA-binding and pharmacokinetic analyses of new sulfonamide bearing thiazolidin-4-ones

Abstract

In this work, Schiff bases and Thiazolidin-4-ones, were synthesized using Sonication and Microwave techniques, respectively. The Schiff base derivatives (3a–b) were synthesized via the reaction of Sulfathiazole (1) with benzaldehyde derivatives (2a–b), followed by the synthesis of 4-thiazoledinone (4a–b) derivatives by cyclizing the synthesized Schiff bases through thioglycholic acid. All the synthesized compounds were characterized by spectroscopic techniques such as FT IR, NMR and HRMS. The synthesized compounds were tested for their in vitro antimicrobial and antioxidant and in vivo cytotoxicity and hemolysis ability. The synthesized compounds displayed better antimicrobial and antioxidant activity and low toxicity in comparison to reference drugs and negative controls, respectively. The hemolysis test revealed the compounds exhibit lower hemolytic effects and hemolytic values are comparatively low and the safety of compounds is in comparison with standard drugs. Theoretical calculations were carried out by using the molecular operating environment (MOE) and Gaussian computing software and observations were in good agreement with the in vitro and in vivo biological activities. Petra/Osiris/Molinspiration (POM) results indicate the presence of three combined antibacterial, antiviral and antitumor pharmacophore sites. The molecular docking revealed the significant binding affinities and non-bonding interactions between the compounds and Erwinia Chrysanthemi (PDB ID: 1SHK). The molecular dynamics simulation under in silico physiological conditions revealed a stable conformation and binding pattern in a stimulating environment.

Highlights

• New series of Thaiazolidin-4-one derivatives have been synthesized.

• Sonication and microwave techniques are used.

• Antimicrobial, Antioxidant, cytotoxicity, and hemolysis activities were observed for all synthesized compounds.

• Molecular Docking and DFT/POM analyses have been predicted.

Communicated by Ramaswamy H. Sarma

Keywords:

• Schiff base
• biological evaluation
• Lipinski’s rule of five′
• molecular docking
• pharmacophore sites
• Veber’s rule

Acknowledgments

Authors are thankful to Head, Department of Chemistry, College of Science, University of Raparin, Sulaymaniyah-Iraq for providing necessary chemical laboratory facilities. The author S. Ahmed. gratefully acknowledges the Council of Scientific and Industrial Research (CSIR), New Delhi, India, for providing financial assistance in the form of Senior Research Fellowship (SRF, File No.: 08/743(001)/2020-EMR-I), which supported the study.

Author’s contributions

S. Hassan, D.M. Aziz, M.N. Abdullah: designed the experiments, analyzed the data, conducted bioactivities studies and wrote the manuscript. F.A. Almalki and M. H Abdellatif: English correction, validation of article and improve the manuscript, edited the final version. R.S. Dongre: Interpretation of spectroscopic data. A.R. Bhat and T. Ben Hadda: POM analyses and interpretation of results. M. Berredjem and S.M.A. Kawsar: performed the molecular Docking. S. A. Sheikh: Molecular dynamics simulations. A.K. Rahiman: Conceptualization, Data Curation and visualization. J. Jamalis and S. Ahmed: Validation, Writing—review & editing. All authors approved the manuscript.

Disclosure Statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Authors are thankful to Head, Department of Chemistry, College of Science, University of Raparin, Sulaymaniyah-Iraq for providing necessary chemical laboratory facilities. The author S. Ahmed. gratefully acknowledges the Council of Scientific and Industrial Research (CSIR), New Delhi, India, for providing financial assistance in the form of Senior Research Fellowship (SRF, File No.: 08/743(001)/2020-EMR-I), which supported the study.