Synthesis And Biological Activity Of 1,4-pentadien-3-one (oxime) Ether Compounds Containing Quinazole(oxa)line Group

As important curcumin analogs,penta-1,4-diene-3-ones have been widely researched and used in medicinal and agrochemical development because of their extensive biological properties,including antibiotic,anticancer,anti-oxidative,anti-inflammatory,antiviral and insecticidal activities.Notably,their visible antiviral activities against plant viruses have been reported well in recently.Quinazoline is a kind of nitrogen-containing fused heterocyclic compounds.Due to its variability of structure and extensive biological activity,quinazoline has gradually become a hot spot in drug creation.In terms of pesticides,quinazoline compounds have biological activities such as antibacterial,antiviral,and acaricidal properties.Quinoxalines are an important class of aromatic benzopyrazine heterocycles.Many quinoxaline derivatives have anti-cancer,anti-bacterial and other activities.On the other hand,oxime ether compounds not only have the characteristics of high efficiency,broad spectrum,and unique mode of action,but also have the advantages of low toxicity,low residue and play an important role in the control of plant diseases in agricultural production.Therefore,we changed the carbonyl group in penta-1,4-diene-3-ones structure to oxime ether structure,and designed and synthesized penta-1,4-diene containing quinazoline or quinoxaline structure in 46 molecules respectively.3-ketooxime ether compounds,all of which were confirmed by ¹H NMR,¹³C NMR and HRMS or ESI-MS.The resulting compounds were tested for anti-plant viral activity using the hemiploid method.The bioassay results showed that the compounds M4,M6,M16,N10,N12,N13,N14,and N20 were at a drug concentration of 500?g/mL.The tobacco mosaic virus has better therapeutic activity,and the inhibition rates are 62.5,55.5,57.9,68.2,57.2,61.0,53.6 and 54.5%,respectively,and better than Ningnanmycin?52.9%?.Compounds M1 and N18 had better protective effects,and the inhibition rates were 70.6%and 65.3%,respectively,superior to Ningnanmycin?64.8%?.The inhibitory rate in the passivation activity was slightly lower than that of Ningnanmycin?90.5%?from 52.5%-82.4%.Using the commercial agents bismerthiazol as the control under the same conditions,the antibacterial activities of some title compounds against tobacco bacterial wilt,Xanhomonas axonopodis pv.citr and Xanthomonas oryzae pv.oryzae at concentration of 100 and 50?g/mL were evaluated based on the turbidimeter test.The results showed that the compounds had a certain inhibitory activity at the concentration of 100 and 50?g/mL,At the concentration of 100?g/mL,compounds M1,M6,M10,M18 and M21 had higher inhibitory activity against Xanhomonas axonopodis pv.citr,which than Bismerthiazol?70.53%?.At the concentration of 50?g/mL,the inhibitory activities of compounds M1,M2,M3,M5,M6,M9,M10,M19,M21 and M25 against Xanhomonas axonopodis pv.citr were higher than that of Bismerthiazol?48.97%?.At the concentration of 100?g/mL,compounds M2,M3,M4,M6,M9,M12,M20,M22,M23 and M24 showed better inhibitory activity against Xanthomonas oryzae pv.oryzae were higher than that of Bismerthiazol?54.38%?.Among them,compounds N4 and N15 had good inhibitory activity against Xanhomonas axonopodis pv.citr.The inhibitory rate of compound N4 at 100?g/mL and 50?g/mL was 99.72%and 60.70%,respectively,which was higher than that of Bismerthiazol?70.53%,48.97%?.MTT assay was used to test the anti-tumor activity of some of the target compounds.Gemcitabine was the control agent.The test results show that most of the target compounds exhibited good inhibitory activity against hepatoma SMMC-7721cells at test concentrations of 1?M and 10?M.At a concentration of 10?M,the inhibitory activity of compound N3 on hepatoma SMMC-7721 cells reached 100.00%,which was much better than the control agent gemcitabine?42.52%?.At a concentration of 1?M,the compound N3 inhibited the growth of hepatoma SMMC-7721 cells.The cells showed good inhibitory activity and the inhibition rate was higher than that of the control agent gemcitabine?20.16%?.In particular,compounds M1,M5,M6,M7,M9,M10,N3,and N4 exhibited excellent inhibitory activity against hepatoma SMMC-7721 cells,and their inhibitory activity was>90.00%,far superior to gemcitabine?20.16%?.