Synthesis Of Chalcone Derivatives Containing Quinazoline Sulfide And Their Antiviral Activity

Chalcones possessed a broad spectrum of biological activities, including antiinflammatory, antioxidant, antibacterial, insecticidal and antiviral activities. Quinazolinone and its derivatives showed broad spectrum of biological properties. In the previous studies of our group, a series of quinazoline derivatives were designed and synthesized, some of them were found to exhibit good antiviral activities. In order to search for highly active antiviral compounds, we attempted to incorporate a quinazolinone unit into the backbone of chalcone through a thioether bond. Twentyone chalcone derivatives containing 4-thioquinazoline moiety were synthesized by using active groups splicing method of active functional group quinazoline introduced into chalcone. The structures of all title compounds were confirmed by IR, 1H NMR, 13 C NMR and elemental analysis. The general contents of all studied are listed as follows:1. The reaction conditions of synthesizing title compounds was optimized, involving the investigation of reaction solvents, acid binding agent, reaction temperature, and charge ratio. Effects of reaction conditions were investigated and the optimal conditions for the reaction are as follows: DMF as reaction solvent, KOH as acid binding agent, n(quinazoline-4-thiol) : n(Intermediates Z) : n(basic) = 1: 0.8: 1.2, and reaction temperature of 40 °C.2. The Half-leaf method was used to determine the in vivo efficacy of the title compounds against tobacco mosaic virus(TMV). The bioassay results showed that most of these compounds exhibited good to excellent anti-TMV activites. In particular, compounds M2 and M6 possessed appreciable protection activities against TMV in vivo, with 50% effective concentration(EC50) values of 138.1 and 154.8 μg/m L, respectively, which were superior to that of Ningnanmycin(191.6 μg/mL).3. The structure-activity relationship(SAR) of the compounds was studied using the three-dimensional quantitative structure-activity relationship(3D-QSAR) method of comparative molecular field analysis(CoMFA) based on the protection activities against TMV EC50 values. The results demonstrated that the CoMFA model exhibited good predictive ability with the non-cross-validated r2 and cross-validated q2 values of 0.993 and 0.674, respectively.