Synthesis And Biological Activity Research Of Quinoxaline Phenylhydrazone Derivaties And Cinnamic Amide Derivaties

Quinoxaline 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. A lot of members of this family have been utilized, playing key roles in new drug or agrochemical R&D. In the first section of this article, substituted phenylhydrazone groups were linked to the quinoxaline scaffold to derive26compounds (6a-6z).’H-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 of6x. Determination of the inhibitory activities of compounds6a-6z against4plant-pathogenic fungi (Rhizoctonia solani, Fusarium graminearum, Sclerotinia sclerotiorum and Phytophthora capsici) was performed. Most of the compounds show great antifungal activities against R. solani. The EC50value of the most potent compound6p is0.16μg/mL, more effective than the positive control Carbendazim (1.42μg/mL). In order to investigate their antioxidant activities, DPPH and lipid peroxidation (LPO) evaluations were performed. Most of these compounds exhibit excellent activities with the lowest IC50being7.60μg/mL (6a, DPPH) and0.96μg/mL (6e, LPO), while the positive control Trolox being5.90μg/mL (DPPH) and18.23μg/mL (LPO).Cinnamic acid and its derivatives are naturally occurring widely and are important intermediates in chemical industry. Since their various biological activities such as antitumor, antifungal and antioxidant, these derivatives show special interest in new chemical R&D. Modifications of the scaffold are widely applied in pharmacy, agrochemical, food, cosmetic and dye industries. Therefore, different substituted phenyl groups are linked to the cinnamic amide scaffold to give22derivatives (2a-2v) in the second part of this article.1H-NMR, MS and elemental analysis were applied to confirm their molecule structures, and X-ray single-crystal diffraction was employed to confirm the crystal structures of2b and2i. Preliminary determination of the inhibitory activities of these compounds against the aforementioned4plant-pathogenic fungi was performed. It’s found that these compounds displayed moderate activities against R. solani in10μg/mL. In addition, evaluation for antiproliferative activities against the human breast cancer cell line MCF-7in vitro was performed and inhibitory activities against EGFR (epidermal growth factor receptor tyrosine kinase) was also conducted by ELISA-kit. These two series of activities show the same trend in general proving that the compounds inhibit the proliferation of the cancer cells mainly through inhibiting the EGFR kinase. Molecular docking of the most potent inhibitor2f into the crystal structure of EGFR complex simulates the probable binding mode in three-dimensional space.