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

• Published in: Journal of biomolecular structure & dynamics Vol. 42; no. 7; pp. 3747 - 3763
• Main Authors: Hassan, Sangar Ali, Aziz, Dara Muhammed, Abdullah, Media Noori, Bhat, Ajmal R., Dongre, Rajendra S., Hadda, Taibi Ben, Almalki, Faisal A., Kawsar, Sarkar M. A., Rahiman, Aziz Kalilur, Ahmed, Sumeer, Abdellattif, Magda H., Berredjem, Malika, Sheikh, S. A., Jamalis, Joazaizulfazli
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.05.2024
• Subjects: Anti-Infective Agents - chemistry; Antineoplastic Agents; Antioxidants - pharmacology; biological evaluation; DNA - chemistry; Hemolysis; Humans; Lipinski's rule of five; molecular docking; Molecular Docking Simulation; pharmacophore sites; Schiff base; Schiff Bases - chemistry; Sulfanilamide; Veber's rule; Schiff base; pharmacophore sites; molecular docking; biological evaluation; Lipinski’s rule of five; Veber’s rule
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2023.2226713

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