Carbohydrate esters are significant in medicinal chemistry because of their efficacy for the synthesis of biologically active drugs. In the present study, methyl β-D-galactopyranoside (MGP) was treated with various acyl halides to produce 6-O-acyl MGP esters by direct acylation method with an excellent yield. To obtain newer products for antimicrobial assessment studies, the 6-O-MGP esters were further modified into 2,3,4-tri-O-acyl MGP esters containing a wide variety of functionalities in a single molecular framework. The chemical structures of the newly synthesized compounds were elucidated by analyzing their physicochemical, elemental, and spectroscopic data. In vitro antimicrobial testing against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) revealed that these MGP estes have promising antifungal functionality compared to their antibacterial activities. The antimicrobial tests demonstrated that the compounds 3 and 10 were the most potent against Bacillus subtilis and Escherichia coli strains, with the minimum inhibitory concentration (MIC) values ranging from 0.352 ± 0.02 to 0.703 ± 0.01 mg/ml and minimum bactericidal concentration (MBC) values ranging from 0.704 ± 0.02 to 1.408 ± 0.04 mg/ml. Density functional theory (DFT) at the B3LYP/3-21G level of theory was employed to enumerate, frontier orbital energy, enthalpy, free energy, electronic energy, MEP, dipole moment which evaluated the effect of certain groups (aliphatic and aromatic) on drug properties. They discovered that all esters were more thermodynamically stable than the parent molecule. Molecular docking is performed using AutoDock Vina to determine the binding affinities and interactions between the MGP esters and the SARS-CoV-2 main protease. The modified esters strongly interact with the prime Cys145, His41, MET165, GLY143, THR26, and ASN142 residues. The MGP esters’ shape and ability to form multiple electrostatic and hydrogen bonds with the active site match other minor-groove binders’ binding modes. The molecular dynamics simulation validates the molecular docking results. The pharmacokinetic characterization of the optimized inhibitor demonstrates that these MGP esters appear to be safer inhibitors and a combination of in silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) prediction and drug-likeness had promising results due to their improved kinetic properties. Structure activity relationships (SAR) study including in vitro and silico results revealed that the acyl chain, palmitoyl (C16) and 4-chlorobenzoyl (4.ClC₆H₄CO-) in combination with sugar were found the most potential activates against human and fungal pathogens. After all, our comprehensive computational and statistical analysis shows that these selected MGP esters can be used as potential inhibitors against the SARS-CoV-2.

碳水化合物酯在药物化学中具有重要意义，因为它们具有合成生物活性药物的功效。在本研究中，甲基 β-D-吡喃半乳糖苷 (MGP) 与各种酰卤化物通过直接酰化法制备 6- O-酰基 MGP 酯，收率良好。为了获得用于抗菌评估研究的更新产品，6 - O -MGP 酯被进一步改性为 2,3,4-tri- O-酰基 MGP 酯，在单个分子框架中含有多种官能团。通过分析其物理化学、元素和光谱数据，阐明了新合成化合物的化学结构。针对五种细菌和两种真菌的体外抗菌测试和物质活性谱的预测 (PASS) 表明，与它们的抗菌活性相比，这些 MGP 酯类化合物具有有希望的抗真菌功能。抗菌测试表明化合物 3 和 10 对枯草芽孢杆菌和大肠杆菌最有效菌株，最小抑菌浓度 (MIC) 值范围为 0.352 ± 0.02 至 0.703 ± 0.01 mg/ml，最小杀菌浓度 (MBC) 值范围为 0.704 ± 0.02 至 1.408 ± 0.04 mg/ml。采用 B3LYP/3-21G 理论水平的密度泛函理论 (DFT) 来枚举前沿轨道能量、焓、自由能、电子能、MEP、偶极矩，评估某些基团（脂肪族和芳香族）对药物性质。他们发现所有的酯都比母体分子在热力学上更稳定。使用 AutoDock Vina 进行分子对接以确定 MGP 酯和 SARS-CoV-2 主要蛋白酶之间的结合亲和力和相互作用。修饰的酯与主要 Cys145、His41、MET165、GLY143、THR26 和 ASN142 残基强烈相互作用。MGP 酯的形状和与活性位点形成多个静电键和氢键的能力与其他小槽粘合剂的结合模式相匹配。分子动力学模拟验证了分子对接结果。优化抑制剂的药代动力学特征表明，这些 MGP 酯似乎是更安全的抑制剂，并且由于其改进的动力学特性，计算机 ADMET（吸收、分布、代谢、排泄和毒性）预测和药物相似性的组合具有可喜的结果. 结构活性关系 (SAR) 研究，包括体外和 优化抑制剂的药代动力学特征表明，这些 MGP 酯似乎是更安全的抑制剂，并且由于其改进的动力学特性，计算机 ADMET（吸收、分布、代谢、排泄和毒性）预测和药物相似性的组合具有可喜的结果. 结构活性关系 (SAR) 研究，包括体外和 优化抑制剂的药代动力学特征表明，这些 MGP 酯似乎是更安全的抑制剂，并且由于其改进的动力学特性，计算机 ADMET（吸收、分布、代谢、排泄和毒性）预测和药物相似性的组合具有可喜的结果. 结构活性关系 (SAR) 研究，包括体外和silico结果显示，酰基链、棕榈酰基 (C16) 和 4-氯苯甲酰基 (4.ClC ₆ H ₄ CO-) 与糖结合是对人类和真菌病原体最有潜力的激活剂。毕竟，我们全面的计算和统计分析表明，这些选定的 MGP 酯可用作抗 SARS-CoV-2 的潜在抑制剂。