New peptide derived antimalaria and antimicrobial agents bearing sulphonamide moiety

Fourteen novel dipeptide carboxamide derivatives bearing benzensulphonamoyl propanamide were synthesized and characterized using 1H NMR, 13C NMR, FTIR and MS spectroscopic techniques. In vivo antimalarial and in vitro antimicrobial studies were carried out on these synthesized compounds. Molecular docking, haematological analysis, liver and kidney function tests were also evaluated to assess the effect of the compounds on the organs. At 200 mg/kg body weight, 7i inhibited the multiplication of the parasite by 81.38% on day 12 of post-treatment exposure. This was comparable to the 82.34% reduction with artemisinin. The minimum inhibitory concentration (MIC) in µM ranged from 0.03 to 2.34 with 7h having MIC of 0.03 µM against Plasmodium falciparium. The in vitro antibacterial activity of the compounds against some clinically isolated bacteria strains showed varied activities with some of the new compounds showing better activities against the bacteria and the fungi more than the reference drug ciprofloxacin and fluconazole.

本研究合成并表征了14种带有苯磺酰基丙酰胺（benzensulphonamoyl propanamide）结构的新型二肽羧酰胺衍生物，采用氢核磁共振波谱（1H NMR）、碳核磁共振波谱（13C NMR）、傅里叶变换红外光谱（FTIR）及质谱（MS）等波谱技术完成结构表征。对上述合成化合物开展了体内抗疟活性与体外抗菌活性研究；此外还通过分子对接（molecular docking）、血液学分析（haematological analysis）、肝肾功能检测（liver and kidney function tests）等手段，评估了该类化合物对机体脏器的影响。在200 mg/kg体重的给药剂量下，化合物7i在给药后第12天对疟原虫增殖的抑制率达81.38%，与青蒿素（artemisinin）82.34%的抑制率相当。该类化合物针对恶性疟原虫（Plasmodium falciparium）的最低抑菌浓度（MIC，minimum inhibitory concentration）区间为0.03~2.34 μM，其中化合物7h的MIC低至0.03 μM。体外抗菌实验结果显示，该类化合物对部分临床分离细菌菌株具有各异的抗菌活性，部分新化合物对细菌与真菌的抑制效果优于对照药物环丙沙星（ciprofloxacin）与氟康唑（fluconazole）。