Abstract

In pharmaceutical industry, the prodrug approaches and drug-drug conjugates are being now vastly used to optimize the efficacy of the drugs for multipurpose. The combination or conjugation of antimicrobials agents with natural antimicrobials may lead to better synergistic antimicrobial activity. Currently, many publications show the potential of ionic liquids (ILs) as novel antimicrobials and even as active pharmaceutical ingredients. The current study showed the synthesis of novel pyrrolidinium-based ILs (C_x, x = 4, 6, 8, 10, 12) and their antibacterial activity alone and in combination with antimicrobial peptide, melittin (MEL), against clinically relevant microorganism, E. coli and S. aureus. The cytotoxicity of synthesized ILs was administered on HEK 293 cell line using MTT assay. The obtained results showed the dependency of antibacterial activity of ILs on alkyl chain length (C4 < C6 < C8 < C10 < C12). The remarkable improvement in the antibacterial efficiency of MEL was seen with ILs; however, antibacterial effect is more pronounced with IL having large alkyl chain length (C₈, C₁₀, and C₁₂) at their minimal concentration with MEL to disrupt the cell membrane. In addition, the binding study and haemocompatibility results showed favourable biocompatibility and stability which could potentially improve its utility for the biomedical field.

Key points

• The combination of melittin and pyrrolidinium-based ILs showed improved antibacterial activity against E. coli and S. aureus which may be used for developing new antibacterial agents.

• Moreover, the cytotoxicity and haemocompatibility results showed excellent biocompatibility of the combinations on human cell line and human serum albumin, respectively, which could potentially improve its utility for the biomedical field.

中文翻译：

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N-甲基取代的吡咯烷鎓类离子液体和蜂毒肽对革兰氏阳性和革兰氏阴性细菌的协同抗菌活性

摘要

在制药工业中，前药方法和药物-药物结合物现在被广泛用于优化多用途药物的功效。抗微生物剂与天然抗微生物剂的组合或结合可导致更好的协同抗微生物活性。当前，许多出版物显示了离子液体（ILs）作为新型抗菌剂甚至是活性药物成分的潜力。当前的研究表明，新型基于吡咯烷鎓的ILs（C _x，x = 4、6、8、10、12）的合成及其与抗菌肽蜂毒肽（MEL）结合使用对临床相关微生物的抗菌活性，大肠杆菌和金黄色葡萄球菌。使用MTT测定法在HEK 293细胞系上施用合成的IL的细胞毒性。获得的结果表明ILs的抗菌活性对烷基链长度的依赖性（C4 ＜C6 ＜C8 ＜C10 ＜C12）。ILs可以明显改善MEL的抗菌效率。然而，对于具有最大烷基链长度（C ₈，C ₁₀和C ₁₂）的IL而言，其最低浓度与MEL一起破坏细胞膜时，其抗菌作用更为明显。另外，结合研究和血液相容性结果显示出良好的生物相容性和稳定性，这可能潜在地提高其在生物医学领域的实用性。

关键点

•蜂毒肽和吡咯烷鎓类IL的组合显示出对大肠杆菌和金黄色葡萄球菌的抗菌活性得到改善，可用于开发新的抗菌剂。

•此外，细胞毒性和血液相容性结果显示，该组合分别在人细胞系和人血清白蛋白上具有出色的生物相容性，这有可能提高其在生物医学领域的效用。