Design, Synthesis, Antibacterial, and Antifungal Evaluation of a New Series of Quinazoline – Thiazole and/or Quinazoline – Triazole Hybrids as Bioactive Heterocycles
Mahmoud El‐Shahat, Nashwa Tawfek, Walaa I. El-Sofany
Abstract
Abstract Herein, a one‐pot reaction between cyclohexanone, thiourea, and 2,5‐dimethoxybenzaldehyde allowed to prepare hexahydroquinazoline‐2( 1H )‐thione 4 firstly, which followed by reacting with hydrazine hydrate to produce the corresponding 2‐hydrazinylhexahydroquinazoline 6 . Interesting analogs of thiazolo[3,2‐ a ]quinazoline 713 where obtained when hexahydroquinazoline‐2( 1H )‐thione 4 reacted with 1,2‐dibromoethane, chloroacetyl chloride, bromoacetic acid, bromoacetic acid/4‐chlorobenzaldehyde, 2‐bromopropionic acid, ethyl bromo cyanoacetate, and/or bromomalononitrile; respectively. While triazolo[4,3‐ a ] quinazoline 14 – 16 were created when 2‐hydrazinylhexahydroquinazoline 6 reacted with triethyl orthoformate, acetic anhydride, and carbon disulfide respectively. Numerous spectroscopy tests, including FT‐IR, NMR ( 1 H & 13 C), and MS spectrum, proved all the newly produced analogs. Additionally, the new analogs were examined for their antibacterial and antifungal properties against Escherichia coli , Staphylococcus aureus , and Candida albicans . It was discovered that triazolo[4,3‐ a ] quinazoline analogs 14 – 16 have superior bacterial and fungal activity when compared to the corresponding conventional doses of Streptomycin andGriseofulvin. Towards Candida albicans ; compounds 14 , 15 , and 16 increase activity with 1.14 %, 1.15 %, and 1.21 %, respectively more than griseofulvin.While, for Staphylococcus aureus ; compounds 14 , 15 , and 16 increase activity with 1.5 %, 1.5 %, and 1.7 %, respectively more than streptomycin. Morever, for Escherichia coli ; compounds 14 , 15 , and 16 increase activity with 1.19 %, 1.21 %, and 1.22 %, respectively more than streptomycin. Finally, structure activity relationships show that quinazoline derivatives exhibit higher activity when fused to pyrazole ring 14–16 as compared when fused thiophene ring 7–13 .