Val-Val二肽-磺酰胺偶联物的合成和生物学评价,Archiv der Pharmazie

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Val-Val二肽-磺酰胺偶联物的合成和生物学评价
Archiv der Pharmazie ( IF 4.3 ) Pub Date : 2020-05-11 , DOI: 10.1002/ardp.202000074
James A Ezugwu _{1,

2} , Uchechukwu C Okoro ₁ , Mercy A Ezeokonkwo ₁ , Chinaraju Bhimapaka ₂ , Sunday N Okafor ₃ , David I Ugwu ₁ , Daniel I Ugwuja ₄

Affiliation

本研究报道了新型 Val-Val 二肽-苯磺酰胺偶联物。这些是通过对位取代的苯磺酰基链烷酰胺与 2-氨基-4-甲基-N-取代的苯基丁酰胺使用经典的肽偶联剂进行缩合反应来实现的。使用傅里叶变换红外、1H-核磁共振 (NMR)、13C-NMR 和电喷雾电离-高分辨率质谱光谱技术对化合物进行表征。正如计算机研究预测的那样，Val-Val 二肽-苯磺酰胺偶联物表现出与标准药物类似的抗疟和抗氧化特性。评价合成的化合物对伯氏疟原虫的体内抗疟活性。还对合成的化合物进行了血液学分析。在 50 毫克/公斤体重时，在治疗后暴露的第 7 天，化合物 8a、8d 和 8g-i 抑制了 48-54% 的寄生虫繁殖，而青蒿素则抑制了 67%。所有合成的二肽都具有良好的抗氧化性能，但与维生素 C 相比较差。本文报道的二肽显示出降低疟疾寄生虫引起的氧化应激的能力。

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Synthesis and biological evaluation of Val–Val dipeptide–sulfonamide conjugates

Novel Val–Val dipeptide–benzenesulfonamide conjugates were reported in this study. These were achieved by a condensation reaction of p‐substituted benzenesulfonamoyl alkanamides with 2‐amino‐4‐methyl‐N‐substituted phenyl butanamide using classical peptide‐coupling reagents. The compounds were characterized using Fourier transform infrared, 1H‐nuclear magnetic resonance (NMR), 13C‐NMR, and electrospray ionization–high‐resolution mass spectrometry spectroscopic techniques. As predicted from in silico studies, the Val–Val dipeptide–benzenesulfonamide conjugates exhibited antimalarial and antioxidant properties that were analogous to the standard drug. The synthesized compounds were evaluated for in vivo antimalarial activity against Plasmodium berghei. The hematological analysis was also conducted on the synthesized compounds. At 50 mg/kg body weight, compounds 8a, 8d, and 8g–i inhibited the multiplication of the parasite by 48–54% on Day 7 of posttreatment exposure, compared with the 67% reduction with artemisinin. All the synthesized dipeptides had a good antioxidant property, but it was less when compared with vitamin C. The dipeptides reported herein showed the ability to reduce oxidative stress arising from the malaria parasite.

更新日期：2020-05-11

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