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Aroyl-isothiocyanates/isoselenocyanates as precursors to obtain novel cis-3-aroyl-thiourea/urea-β-lactams: design, synthesis, docking and biological evaluation

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Aroyl-isothiocyanates/isoselenocyanates as precursors to obtain novel cis-3-aroyl-thiourea/urea-β-lactams: design, synthesis, docking and biological evaluation
 
Creator Kumar, Pankaj
Kaur, Jaswinder
Kumari, Sumeeta
Paliwal, Sakshi
Berry, Shiwani
Pinnaka, Anil Kumar
Bhalla, Aman
 
Subject QR Microbiology
 
Description Herein, a novel synthetic methodology was devised to synthesize cis-3-aroyl-urea-β-lactams by reacting aroyl isoselenocyanates with cis-3-amino-β-lactams in a THF : H2O mixture (9 : 1). This synthetic approach eliminates the previous requirement for the challenging synthesis of unstable aroyl isocyanates and the low-yield acylation of urea to obtain aroyl urea derivatives. Further optimized conditions for nucleophilic reaction of aroyl isothiocyanates with cis-3-amino-β-lactams to obtain cis-3-aroyl-thiourea-β-lactams were developed. The stereochemistry of cis-3-aroyl-thiourea/urea-β-lactams (5a–f/8a–f) was elucidated by analyzing the J values of C3–H and C4–H of β-lactams. Subsequently, we evaluated the antibacterial activity of these compounds against both Gram-positive bacteria (S. aureus and B. cereus) and Gram-negative bacteria (P. aeruginosa and E. coli). Remarkably, among all the synthesized compounds, 8e exhibited potent activity against all bacterial strains, with a notable MIC value of 6.25 μg mL−1 against B. cereus, surpassing ampicillin (MIC = 25 μg mL−1) by four-fold. Additionally, compounds 8d and 8e demonstrated promising antifungal properties, with an MIC value of 1.5 μg mL−1 against C. tropicalis, comparable to fluconazole (MIC = 1 μg mL−1). Furthermore, compounds 8d and 8e exhibited 80% and 75% cell viability against THLE-2 cells at a concentration of 25 μg mL−1. Molecular docking analysis provided additional support for the observed in vitro antibacterial and antifungal activities of compound 8e.
 
Publisher RSC Publishing
 
Date 2023-11-16
 
Type Article
PeerReviewed
 
Relation https://pubs.rsc.org/en/content/articlelanding/2024/nj/d3nj04485h
http://crdd.osdd.net/open/3187/
 
Identifier Kumar, Pankaj and Kaur, Jaswinder and Kumari, Sumeeta and Paliwal, Sakshi and Berry, Shiwani and Pinnaka, Anil Kumar and Bhalla, Aman (2023) Aroyl-isothiocyanates/isoselenocyanates as precursors to obtain novel cis-3-aroyl-thiourea/urea-β-lactams: design, synthesis, docking and biological evaluation. New Journal of Chemistry, 48. pp. 67-78.