某些带有酯官能团的新型苯并二恶唑-咪唑分子杂化物的合成、结构解析及抗真菌潜力

Synthesis, structure elucidation, and antifungal potential of certain new benzodioxole-imidazole molecular hybrids bearing ester functionalities.

作者信息

Al-Wabli Reem I, Al-Ghamdi Alwah R, Ghabbour Hazem A, Al-Agamy Mohamed H, Attia Mohamed I

机构信息

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia,

Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.

出版信息

Drug Des Devel Ther. 2019 Feb 26;13:775-789. doi: 10.2147/DDDT.S199135. eCollection 2019.

DOI:10.2147/DDDT.S199135

PMID:30880911

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6396673/

Abstract

BACKGROUND

The incidence of fungal infections is a growing serious global health burden. There is an urgent medical demand to acquire new antifungal drug-like compounds having azole nuclei to get rid of the drawbacks of the currently available azole antifungal agents.

METHODS

The target compounds were synthesized in a four-step reaction sequence using the appropriate acetophenone derivative as a starting material. The antifungal potential of the title compounds was assessed using DIZ and MIC assays according to the reported standard procedures.

RESULTS

The newly synthesized oximino esters were identified with the aid of various spectroscopic approaches. Their assigned chemical structures were confirmed via single-crystal X-ray structure of compound . The molecular structure of compound was crystallized in the triclinic, -1, =9.898 (3) Å, =10.433 (3) Å, =11.677 (4) Å, =86.886 (6)°, =87.071 (7)°, =64.385 (6)°, =1,085.2 (6) Å3, =2. The synthesized compounds were in vitro evaluated for antifungal potential against four fungal strains. Compounds and bearing a trifluoromethylphenyl moiety showed the best anti- activity with minimum inhibitory concentration (MIC) value of 0.148 μmol/mL, while compound displayed the best activity toward with MIC value of 0.289 μmol/mL. Compounds and were the most active congeners against Candida parapsilosis and , respectively.

CONCLUSION

Single-crystal X-ray analysis of compound confirmed without doubt the assigned chemical structures of the title compounds as well as confirmed the ()-configuration of their oximino group. Compounds and emerged as the most active compounds against the tested fungi and they could be considered as new antifungal lead candidates.

摘要

背景

真菌感染的发生率正成为日益严重的全球健康负担。迫切需要获得具有唑核的新型抗真菌类药物化合物，以克服现有唑类抗真菌药物的缺点。

方法

以适当的苯乙酮衍生物为起始原料，通过四步反应序列合成目标化合物。根据报道的标准程序，使用纸片扩散法（DIZ）和最低抑菌浓度（MIC）测定法评估标题化合物的抗真菌潜力。

结果

借助各种光谱方法鉴定了新合成的肟基酯。通过化合物的单晶X射线结构确认了它们指定的化学结构。化合物的分子结构以三斜晶系结晶，(a = 9.898(3) Å)，(b = 10.433(3) Å)，(c = 11.677(4) Å)，(\alpha = 86.886(6)°)，(\beta = 87.071(7)°)，(\gamma = 64.385(6)°)，(V = 1085.2(6) Å^3)，(Z = 2)。对合成的化合物进行体外抗四种真菌菌株的抗真菌潜力评估。带有三氟甲基苯基部分的化合物和表现出最佳的抗活性，最低抑菌浓度（MIC）值为(0.148 μmol/mL)，而化合物对表现出最佳活性，MIC值为(0.289 μmol/mL)。化合物和分别是对近平滑念珠菌和最具活性的同系物。