新型α-取代磺酰胺：乙酰胺衍生物作为二氢叶酸还原酶（DHFR）抑制剂的设计、合成及生物学评价

Design, synthesis, and biological evaluation of novel -substituted sulfonamides: acetamides derivatives as dihydrofolate reductase (DHFR) inhibitors.

作者信息

Hussein Essam M, Al-Rooqi Munirah M, Abd El-Galil Shimaa M, Ahmed Saleh A

机构信息

1Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah, 21955 Saudi Arabia.

2Chemistry Department, Faculty of Science, Assiut University, Assiut, 71516 Egypt.

出版信息

BMC Chem. 2019 Jul 11;13(1):91. doi: 10.1186/s13065-019-0603-x. eCollection 2019 Dec.

BACKGROUND

Sulfonamide derivatives are of great attention due to their wide spectrum of biological activities. Sulfonamides conjugated with acetamide fragments exhibit antimicrobial and anticancer activities. The inhibition dihydrofolate reductase (DHFR) is considered as one of the most prominent mechanism though which sulfonamide derivatives exhibits antimicrobial and antitumor activities.

RESULTS

In this study, a new series of 2-(arylamino)acetamides and -arylacetamides containing sulfonamide moieties were designed, synthesized, characterized and assessed for their antimicrobial activity and screened for cytotoxic activity against human lung carcinoma (A-549) and human breast carcinoma (MCF-7) cell lines. A molecular docking study was performed to identify the mode of action of the synthesized compounds and their good binding interactions were observed with the active sites of dihydrofolate reductase (DHFR).

CONCLUSION

Most of the synthesized compounds showed significant activity against A-549 and MCF-7 when compared to 5-Fluorouracil (5-FU), which was used as a reference drug. Some of these synthesized compounds are active as antibacterial and antifungal agents.

背景

磺胺衍生物因其广泛的生物活性而备受关注。与乙酰胺片段共轭的磺胺表现出抗菌和抗癌活性。抑制二氢叶酸还原酶（DHFR）被认为是磺胺衍生物展现抗菌和抗肿瘤活性的最显著机制之一。

结果

在本研究中，设计、合成、表征了一系列新的含磺胺部分的2-（芳基氨基）乙酰胺和芳基乙酰胺，并评估了它们的抗菌活性，同时筛选了其对人肺癌（A-549）和人乳腺癌（MCF-7）细胞系的细胞毒性活性。进行了分子对接研究以确定合成化合物的作用模式，并观察到它们与二氢叶酸还原酶（DHFR）的活性位点有良好的结合相互作用。