Synthesis And Biological Activity Research Of 1,3,4-Oxadiazole Derivaties And Nicotinamide Derivaties

1,3,4-oxadiazole and its derivatives show nearly all ranges of biological activities, such as antioxidant, antibacterial, antifungal, herbicide, pesticide, antitumor, antitubercular, antileishmanial, antimalarial, antidepressant and immunosuppressive activities. In the first section of this article,1,3,4-substituted oxadiazole was used as molecular skeleton, 1,4-benzodioxan and mannich base were introduced in molecular, synthesis 30 novel compounds (6a-6ae).1H-NMR, MS along with elemental analysis were applied to confirm their molecule structures, and X-ray single-crystal diffraction was employed to confirm the crystal structure of 6b. All compounds was tested antioxidant activity by DPPH, ABTS+ and FRAP method and the antioxidant activity data pretty good. Antioxidant activity of 6e and 6f was better than commonly used antioxidants BHT and Trolox. Four strong activity compounds (6a,6e,6f,6w) and three weak activity (6t,6u,6w) compounds were picked to do further research. Their antioxidant activity was tested by two chemical simulation biological methods-inhibition of microsomal lipid peroxidation (LPO) and protection against 2,2’-azobis (2-amidinopropane hydrochloride) (AAPH) induced DNA strand breakage.6f and 6e were still demonstrated as the most potent antioxidative compounds. Determination of the inhibitory activities of compounds 6a-6ae against Rhizoctonia solani and Sclerotinia sclerotiorum was performed. Most of the compounds show good antifungal activities against S. sclerotiorum, the EC50 value of compound 6b was 13.7 μM which is eqauled to half effect of carbendazim.Nicotinic acid, its derivatives are occurring widely in natrual product and are important intermediates in chemical industry. In the second part of this paper, with the structure of boscalid as reference, we synthesis 37 compounds started from 2-mercaptonicotinic acid and introduce N-phenyl amide into target structure.1H-NMR, MS and elemental analysis were applied to confirm their molecule structures. Determination of the inhibitory activities of these compounds against the aforementioned 2 plant-pathogenic fungi was performed and displayed moderate activities, the EC50 value of compound 3a-17 were 15.8 μM and 20.3μM, respectively. Meanwhile, inhibition activities against two fungal SDH were tested and achieved the same tendency with the data acquired from in vitro antifungal assay, it’s explains the target of this series of compounds reasonably. Homology building and molecular docking were used to study the complex of 3a-17 and the target protein, the result shows amino acid residues of recepter interacted with 3a-17 by many bonging such as hydrogen bonding and hydrophobic interaction.