Khan Sher Wali, Rashid Haroon Ur, Nayab Saira, Khan Momin, Rasheed Lubna
Department of Chemistry, Rawalpindi Women University, Satellite Town Rawalpindi, Pakistan; Department of Chemistry, Shaheed Benazir Bhutto University, Sheringal, Dir Upper 18150, Pakistan.
Center for Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas, Pelotas, RS, Brazil.
Comput Biol Chem. 2025 Dec;119:108565. doi: 10.1016/j.compbiolchem.2025.108565. Epub 2025 Jun 18.
This study reports the synthesis and assessment of a series of imide derivatives of phthalic anhydride (phthalimides) for their potential antimicrobial activities. Phthalic acid was first converted into phthalic anhydride using acetic anhydride, which was then reacted with various L-amino acids to obtain phthalimides in high yields. Compounds HUPB, HUPC, HUPF, and HUPH exhibited promising antimicrobial activity, with HUPF and HUPH being the most potent. HUPF exhibited significant antimicrobial activity, showing inhibition zones of 24 mm versus Staphylococcus aureus (at 2000 µg/mL), 17 mm versus Escherichia coli (at 2000 µg/mL), and 18 mm against Candida albicans (at 1000 µg/mL). The minimum inhibitory concentrations (MICs) were 16 µg/mL, 24 µg/mL, and 24 µg/mL for S. aureus, E. coli, and C. albicans, respectively. HUPH demonstrated strong antimicrobial activity, exhibiting inhibition zones of 23 mm versus S. aureus, 19 mm versus E. coli, and 20 mm versus C. albicans, with corresponding MICs of 20 µg/mL, 28 µg/mL, and 20 µg/mL, respectively. Molecular docking reinforced these results, demonstrating effective bindings for HUPF and HUPH, suggesting their potential as antimicrobial agents. Both compounds adhered to Lipinski's Rule of Five, signifying decent oral bioavailability, gastrointestinal absorption (≥0.55), and no PAINS (pan-assay interference compounds) alerts. Density functional theory (DFT) calculations revealed that HUPF and HUPH possess narrow HOMO-LUMO energy gaps and elevated dipole moments, indicating high chemical reactivity, and strong polarity, which further support their enhanced antimicrobial potential. These results highlight the therapeutic potential of the two compounds for further development as novel antimicrobial agents.
本研究报告了一系列邻苯二甲酸酐的酰亚胺衍生物（邻苯二甲酰亚胺）的合成及其潜在抗菌活性评估。邻苯二甲酸首先用乙酸酐转化为邻苯二甲酸酐，然后与各种L - 氨基酸反应，以高收率获得邻苯二甲酰亚胺。化合物HUPB、HUPC、HUPF和HUPH表现出有前景的抗菌活性，其中HUPF和HUPH最为有效。HUPF表现出显著的抗菌活性，对金黄色葡萄球菌（在2000μg/mL时）的抑菌圈为24mm，对大肠杆菌（在2000μg/mL时）为17mm，对白色念珠菌（在1000μg/mL时）为18mm。金黄色葡萄球菌、大肠杆菌和白色念珠菌的最低抑菌浓度（MIC）分别为16μg/mL、24μg/mL和24μg/mL。HUPH表现出较强的抗菌活性，对金黄色葡萄球菌的抑菌圈为23mm，对大肠杆菌为19mm，对白色念珠菌为20mm，相应的MIC分别为20μg/mL、28μg/mL和20μg/mL。分子对接强化了这些结果，证明HUPF和HUPH有有效的结合，表明它们作为抗菌剂的潜力。这两种化合物均符合Lipinski的五规则，表明有良好的口服生物利用度、胃肠道吸收（≥0.55）且无PAINS（泛测定干扰化合物）警示。密度泛函理论（DFT）计算表明，HUPF和HUPH具有狭窄的HOMO - LUMO能隙和较高的偶极矩，表明其具有高化学反应性和强极性，这进一步支持了它们增强的抗菌潜力。这些结果突出了这两种化合物作为新型抗菌剂进一步开发的治疗潜力。
