Synthesis And Bioactivity Of Pentadienone Derivatives Containing Quinazoline Sulfide

1,4-pentadien-3-one, a curcumin derivative, exhibited biological properties, including antiviral activities, antifungal, insecticidal, and anticancer. Quinazolinone and its derivatives showed broad spectrum of biological activities, 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 1,4-pentadien-3-one through a thioether bond. Then we synthesized 27 target compounds K01–K27. The structures of all the target compounds were elucidated by elemental analysis, IR, 1H NMR and 13 C NMR spectra. The results of my findings and all work are outlined below:1 Compound K02 as an modele, the reaction conditions of compounds was optimized, involved with investigation of reaction solvents, material mole ratio, catalysts, reaction temperature and reaction time. The optimized optimal reaction condition was using DMF as reaction solvent, KOH as acid binding agent, n(intermediate 3) : n(intermediate 6) : n(basic) = 1: 0.8: 1.2, under 40 °C stirring for refluxing 4 h.2 The antiviral activities against CMV of the title compounds K01–K27 were tested in vivo using the half leaf method. Most of the title compounds exhibited excellent antiviral activities against tobacco mosaic virus(TMV) and cucumber mosaic virus(CMV) in vivo. Among the title compounds, K10 exhibited the best curative activity against TMV, with a half-maximal effective concentration(EC50) value of 213.5 μg/m L, which was better than that of ningnanmycin(270.9 μg/m L). Meanwhile, K01 showed remarkable protection activity against TMV and curative activity against CMV, with EC50 values of 124.3 and 365.5 μg/m L, respectively, which were superior to those of ningnanmycin(195.1 and 404.9 μg/m L, respectively).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(Co MFA) and comparative molecularsimilarity index analysis(Co MSIA) models were generated based on the curative activities against TMV EC50 values. and exhibited good predictive abilities with cross-validated q2 and non-cross-validated r2 values for Co MFA and Co MSIA of 0.548, 0.647 and 0.994, 0.993, respectively.