Synthesis And Antimicrobial Activity Of Quinazolinones

Nitrogen-containing heterocycles are an integral part of many drug molecules,physiologically active natural products and synthetic compounds.Quinazolinone represents a class of annulated six-membered nitrogen heterocycles and a core structural component in a variety of natural products and synthesized compounds.These compounds show extensively biological and pharmacological activity,for instance,antitumor,anti-inflammatory,antihistamine,antimicrobial and anti-hypertension et al.The synthesis of quinazolinone and its derivatives attracted considerable interests.In this thesis,a new method for synthesis of 2-sulfanylidene-2,3-dihydroquinazoline-4(1H)-ones,quinazoineone Schiff and bis-2,3-dihydroquinazolin-4(1H)-ones were developed and the antimicrobial activity was evaluated.A facile and efficient method was developed for the synthesis of 2-sulfanylidene-2,3-dihydroquinazoline-4(1H)-ones,under ultrasonic irradiation from condensation reaction of isatoic anhydride,hydrazine hydrate,and aromatic aldehydes,which was catalyzed by nano CuO in the solvent of N-methypyrolidone at 70 ?.13 compounds were obtained in good to excellent yield.In order to develop new potent anti-phytopathogenic fungi drugs,the compounds were docked with the protein 2A3 E of chitinase Family 18 using the calculation software AutoDock primarily.All compounds were investigated for anti-phytopathogenic fungi activity via the method of minimum inhibitory concentrations of 9 kinds of phytopathogen.The majority of compounds exhibited a good inhibitory activity to Alternaria brassicae and Colletotrichum gloeosporioides.A new and convenient method was developed via condensation reaction of isatoic anhydride,hydrazine hydrate,and aromatic aldehydes,which was catalyzed by manual synthetic zanthoxylum bungeanum seed oil(ZSO)based solid acid in EtOH at reflux temperature for 5 h.Fifteen quinazolinone Schiff base derivatives were obtained in good to excellent yields.To well understand the influence of the nitrogen source on the yield of target products,the study was extended to ethidene diamine in EtOH at reflux temperature for 5 h,Four bis-2,3-dihydroquinazolin-4(1H)-ones were obtained.All synthesized compounds were screened for their antibacterial activities in vitro against two Gram-negative bacterial strains and two Gram-positive bacterial strains using the minimum inhibitory concentration(MIC)method.The structure-activity relationship(SAR)of the antibacterial activity evaluation against Streptococcus lactis was also explored.In the series of quinazolinone derivatives,the moieties at the C-2 position are especially important for the activity.It was established that combination of quinazolinone with halogenated phenyl,pyridyl,and furanyl was favorable for the against Streptococcus lactis activity.