苯基吡唑缩氨基胍衍生物的合成及其抗菌活性研究

THE SYNTHESIS AND ANTIBACTERIAL ACTIVITY EVALUATION OF ALKYLENE AMINOGUANIDINE DERIVATIVES BEARING PHENYL PARAZOLE

目的设计合成一系列苯基吡唑缩氨基胍衍生物,用于抗菌活性的筛选。方法以苯乙酮与盐酸氨基脲为原料,经亲核加成反应、Vilsmeier-Haack反应、亲核取代反应和缩合反应得最终产物4a～4j和5a～5c。采用连续稀释法评价13个化合物对革兰氏阳性菌和革兰氏阴性菌的抑制活性。结果部分化合物对革兰氏阳性菌和阴性菌显示出一定的抑制活性,其中化合物5c对各种测定菌株均显示出抑制活性,对枯草芽孢杆菌(CMCC 63501)的抑菌活性MIC值达到16μg/mL。结论本研究合成的苯基吡唑缩氨基胍衍生物对所选择的革兰氏阳性菌和阴性菌具有一定的抑制活性,虽然活性强度未能达到预期目的,但该研究进一步丰富了缩氨基胍衍生物的抗菌构效关系,为新的抗菌活性化合物乃至候选药物的发现奠定了基础。

Objective： To design and synthesize a series of alkylene aminoguanidine derivatives bearing phenyl parazole moiety and evaluate their antibacterial activity. Methods： Through nucleophilic addition reaction, Vilsmeier-Haack reaction and condensation reaction, 13 alkylene aminoguanidine derivatives bearing phenyl parazole moiety were synthesized using semicarbazlde hydrochloride and substituted acetophenones as starting materials. The inhibition activity of 13 compounds on gram-positive bacteria and gram-negative bacteria was evaluated by continuous dilution method. Results： Part of target compounds showed inhibitory activity against Gram-positive and Gram-negative strains chosen. Among which, compound 5c showed broad-spectrum antibacterial activity and good inhibitory activity against Bacillus subtilis CMCC 63501 with the minimal inhibitory concentration （MIC） of 16 μg/mL. Conclusion： In the study, alkylene aminoguanidine derivatives bearing phenyl parazole moiety were found with certain antibacterial activity. This found further enrich the structure-activity relationship of alkylene aminoguanidine derivatives, and lay the foundation for the development of new antibacterials.