Rahaman Md Lutfor, Rahman Md Atiqur, Hasnain Md Mohin, Amran Mohammad, Bin Emran Talha, Khan Md Ashikur Rahaman, Patwary Md Abdul Majed, Kazi Mohsin, Matin Mohammed Mahbubul
Bioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong, 4331, Bangladesh.
Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI 02912, USA.
Med Chem. 2025;21(5):385-402. doi: 10.2174/0115734064292665240523113515.
The approval of Sucrose Fatty Acid Esters (SFAEs) as food additives/ preservatives with antimicrobial potential has triggered enormous interest in discovering new biological applications. Accordingly, many researchers reported that SFAEs consist of various sugar moieties, and hydrophobic side chains are highly active against certain fungal species.
This study aimed to conduct aregioselective synthesis of SAFE and check the effect of chain length and site of acylation (i.e., C-6 vs. C-2, C-3, C-4, and long-chain vs. short-chain) on antimicrobial potency.
A direct acylation method maintaining several conditions was used for esterification. tests, molecular docking, and in silico studies were conducted using standard procedures.
tests revealed that the fatty acid chain length in mannopyranoside esters significantly affects the antifungal activity, where C12 chains are more potent against Aspergillus species. In terms of acylation site, mannopyranoside esters with a C8 chain substituted at the C-6 position are more active in antifungal inhibition. Molecular docking also revealed that these mannopyranoside esters had comparatively better stable binding energy and hence better inhibition, with the fungal enzymes lanosterol 14-alpha-demethylase (3LD6), urate oxidase (1R51), and glucoamylase (1KUL) than the standard antifungal drug fluconazole. Additionally, the thermodynamic, orbital, drug-likeness, and safety profiles of these mannopyranoside esters were calculated and discussed, along with the Structure-Activity Relationships (SAR).
This study thus highlights the importance of the acylation site and lipid-like fatty acid chain length that govern the antimicrobial activity of mannopyranoside-based SFAE.
蔗糖脂肪酸酯（SFAEs）作为具有抗菌潜力的食品添加剂/防腐剂获得批准，引发了人们对发现其新生物应用的极大兴趣。因此，许多研究人员报告称，SFAEs由各种糖部分组成，其疏水侧链对某些真菌具有高度活性。
本研究旨在进行SAFE的区域选择性合成，并检查酰化链长度和位点（即C-6与C-2、C-3、C-4，以及长链与短链）对抗菌效力的影响。
采用保持多种条件的直接酰化方法进行酯化。使用标准程序进行测试、分子对接和计算机模拟研究。
测试表明，甘露吡喃糖苷酯中的脂肪酸链长度显著影响抗真菌活性，其中C12链对曲霉菌种的活性更强。就酰化位点而言，在C-6位被C8链取代的甘露吡喃糖苷酯在抗真菌抑制方面更具活性。分子对接还显示，与标准抗真菌药物氟康唑相比，这些甘露吡喃糖苷酯与真菌酶羊毛甾醇14-α-脱甲基酶（3LD6）、尿酸氧化酶（1R51）和葡糖淀粉酶（1KUL）具有相对更好的稳定结合能，因此具有更好的抑制作用。此外，还计算并讨论了这些甘露吡喃糖苷酯的热力学、轨道、类药性和安全性概况，以及构效关系（SAR）。
因此，本研究突出了酰化位点和类脂脂肪酸链长度对基于甘露吡喃糖苷的SFAE抗菌活性的重要性。
