Syntheses And Biological Activities Of Novel Acetophenone Derivatives

In order to exploit efficient antifungal agents and antitumor drugs, to search for a new target for treatment of plant pathogens or cancer, and guide the development of a treatment plant pathogens or new antitumor target drugs, according to the early work of our research group, the side chain and pharmacophore of the acetophenone derivatives were optimized from the commereialized acetophenones and high bioactive compounds the literature reported, by the means of the active structural stitching. This dissertation including as follows:1. One hundrand and sixteen acetophenone derivatives were designed and synthesized by a multiple step synthetic procedures, of which seventy compounds were the first time to report. Their structures were characterized by1H-NMR,13C-NMR, MS spectroseopies. X-ray single crystal analysis is used to confirm the structure of four compounds.2. Optimization for the Synthesis of acetophenone derivatives, especially in the introduction of active moiety to the structure of2-Chloro-3',4'-dihydroxyacetophenone under microwave-assisted, and which enabling us to build a number of ethers of acetophenones library quickly and efficiently.3. The antifungal activities of the title compounds against seven phytopathogenic fungi were evaluated by mycelial rate growth assay, which are Colletotrichum gloeosporiodes, Botrytis cinerea, Alternaria solani,Fusarium oxysporum f.sp. vasinfectum, Fusarium oxysporum f.sp. niveum, Fusarium solani, Fusarium graminearum. Some compounds have good activation of suppressing antifungal activities respectively, especially compound IIIc was found to be the most active and might be a potential lead structure, with IC50values of10-19μg/mL to the seven plant pathogenic fungus, which is much better than contrast hymexazol (IC50=23～95μg/mL); imidazole-containing heterocyclic novel bromoacetophenone oxime ether derivatives are very sensitive to these seven fungus, especially VI g, VI i and VI p on Fusarium solani reached1μg/mL or less, With the IC50values of0.71×0.23μg/mL,0.05±0.01μg/mL and0.06±0.02μg/mL, which might be promising leads for agricultural fungicides.4. The cytotoxic activity of the most synthesized compounds were evaluated to human promyelocytic leukemia cell line (HL-60), human cervical carcinoma cell lines (HeLa) and human hepatoma cell line (HepG2) by the SRB assay, and we succeeded to find several kinds of lead compounds with outstanding activity, which are much better than positive control agent camptothecin. Ester derivatives from2-Chloro-3',4'-dihydroxyacetophenone are very potent to be used as lead structure for the discovery of novel anticancer drug.The results showed that the three tumor cell lines, HL-60, HeLa and HepG2cell, are relatively sensitive to some compounds of3',4'-dihydroxy-2-chlorophenyl ethyl ketone ether and ester derivatives. With the IC50of some compounds are far less than that of the positive control agent camptothecin. Six compounds of3',4'-dihydroxy-2-chloroacetophenone ester derivatives (IVq, Vaa, Vab, Vac, Vah and Vbd) showing excellent activity to HL-60with the IC50value around10μM; Four compounds (V ab, V ad, V ae and V ag) giving excellent activity on the HeLa cell strain than the control drug camptothecin; Twelve compounds (IIIb, IIIf, Vab, Vae, Vaf, Vak, Vbb, Vbc, Vbd, Vbf, Vbg and Vbi) showing excellent cytotoxic activity to HepG2cells with the IC50values are close to the positive control drug campothecin.5. The summary of structure-activity relationship of acetophenone derivatives on antifungal and antitumor activity give important direction for further optimization.