New Arylazo‐Based (Chromene‐Thiazole) Hybrids as Potential MRSA Inhibitors

• Published in: Chemistry & biodiversity 2023-04, Vol.20 (4), p.e202300206-n/a
• Main Authors: Abdallah, Zeinab A., Sanad, Sherif M. H., Mekky, Ahmed E. M., Ahmed, Mohamed S. Mohamed
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Benzopyrans - chemistry; Benzopyrans - pharmacology; Chromene; Ciprofloxacin; Drug resistance; E coli; Escherichia coli; Ethanol; Hybrids; in vitro antibacterial activity; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minimum inhibitory concentration; MRSA inhibitory activity; Multicomponent reactions; Pharmacokinetics; Physicochemical properties; Piperidine; Staphylococcus aureus; Synthesis; Thiazole; Thiazoles - chemistry; Thiazoles - pharmacology
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.202300206

A three‐component protocol was established to efficiently synthesize (chromene‐thiazole) and related arylazo analogs in good to excellent yields. The desired products were prepared by reacting the appropriate salicylaldehydes, 2‐cyanothioacetamide, and chloroacetone or hydrazonyl chlorides. Using piperidine as a mediator in ethanol at 80 °C for 4–6 h, the three‐component protocol produce the target hybrids in 87–96 % yields. The newly synthesized products showed a broad range of antibacterial activity. The addition of an arylazo unit at the chromene‐C6 position significantly improved the antibacterial activity, while the impact of adding an arylazo group at the thiazole‐C5 position varied based on the electronic characteristics of the para‐substituted arene unit. Generally, series that is linked to two arylazo units, one at chromene‐C6 and the other at thiazole‐C5, showed the best activity. Some new hybrids showed effective antibacterial activity than ciprofloxacin with MIC/MBC values up to 1.9/3.9 μM against S. aureus and E. coli. Additionally, they demonstrated better effectiveness against MRSA ATCC:33591 and ATCC:43300 compared to linezolid, with MIC/MBC values up to 4.0/16.1 and 3.9/15.6 μM, respectively. The data predicted for the physicochemical properties, lipophilicity, pharmacokinetics, and drug‐likeness of new arylazo‐based chromene‐thiazole hybrids evaluated by SwissADME. As a result of the above, products that are linked to two arylazo units can be considered drug‐like scaffolds.