Fatima Miraj, Aslam Samina, Zafar Ansa Madeeha, Irfan Ali, Khan Misbahul Ain, Ashraf Muhammad, Faisal Shah, Noreen Sobia, Shazly Gamal A, Shah Bakht Ramin, Bin Jardan Yousef A
Department of Chemistry, The Women University, Multan 66000, Pakistan.
Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
Biomedicines. 2023 Aug 30;11(9):2428. doi: 10.3390/biomedicines11092428.
Furan chalcone scaffolds belong to the most privileged and promising oxygen-containing heterocyclic class of compounds, which have a wide spectrum of therapeutic applications in the field of pharmaceutics, pharmacology, and medicinal chemistry. This research described the synthesis of a series of twelve novel and seven reported furan chalcone (conventional synthetic approach) analogues - through the application of microwave-assisted synthetic methodology and evaluated for therapeutic inhibition potential against bacterial urease enzyme. In the first step, a series of nineteen substituted 5-aryl-2-furan-2-carbaldehyde derivatives - were achieved in moderate to good yields (40-70%). These substituted 5-aryl-2-furan-2-carbaldehyde derivatives - were condensed with acetophenone via Claisen-Schmidt condensation to furnish substituted furan chalcone scaffolds - in excellent yields (85-92%) in microwave-assisted synthetic approach, while in conventional methodology, these furan chalcone - were furnished in good yield (65-90%). Furan chalcone structural motifs - were characterized through elemental analysis and spectroscopic techniques. These nineteen (19)-afforded furan chalcones - were screened for urease inhibitory chemotherapeutic efficacy and most of the furan chalcones displayed promising urease inhibition activity. The most active urease inhibitors were 1-phenyl-3-[5-(2',5'-dichlorophenyl)-2-furyl]-2-propen-1-one with an IC value of 16.13 ± 2.45 μM, and 1-phenyl- 3-[5-(2'-chlorophenyl)-2-furyl] -2-propen-1-one with an IC value of 18.75 ± 0.85 μM in comparison with reference drug thiourea (IC = 21.25 ± 0.15 μM). These furan chalcone derivatives and are more efficient urease inhibitors than reference drug thiourea. Structure-activity relationship (SAR) revealed that the 2,5-dichloro and 2-chloro moiety containing furan chalcone derivatives may be considered as potential lead reagents for urease inhibition. The in silico molecular docking study results are in agreement with the experimental biological findings. The results of this study may be helpful in the future drug discovery and designing of novel efficient urease inhibitory agents from this biologically active class of furan chalcones.
呋喃查尔酮支架属于最具优势和前景的含氧杂环化合物类别，在制药、药理学和药物化学领域具有广泛的治疗应用。本研究描述了通过微波辅助合成方法合成一系列十二种新型和七种已报道的呋喃查尔酮（传统合成方法）类似物，并评估了它们对细菌脲酶的治疗抑制潜力。第一步，以中等至良好的产率（40 - 70%）获得了一系列十九种取代的5 - 芳基 - 2 - 呋喃 - 2 - 甲醛衍生物。这些取代的5 - 芳基 - 2 - 呋喃 - 2 - 甲醛衍生物通过克莱森 - 施密特缩合与苯乙酮缩合，在微波辅助合成方法中以优异的产率（85 - 92%）提供取代的呋喃查尔酮支架，而在传统方法中，这些呋喃查尔酮的产率良好（65 - 90%）。呋喃查尔酮结构基序通过元素分析和光谱技术进行表征。对这十九种得到的呋喃查尔酮进行脲酶抑制化疗功效筛选，大多数呋喃查尔酮显示出有前景的脲酶抑制活性。与参考药物硫脲（IC = 21.25 ± 0.15 μM）相比，最具活性的脲酶抑制剂是1 - 苯基 - 3 - [5 - (2',5' - 二氯苯基) - 2 - 呋喃基] - 2 - 丙烯 - 1 - 酮，IC值为16.13 ± 2.45 μM，以及1 - 苯基 - 3 - [5 - (2' - 氯苯基) - 2 - 呋喃基] - 2 - 丙烯 - 1 - 酮，IC值为18.75 ± 0.85 μM。这些呋喃查尔酮衍生物比参考药物硫脲更有效地抑制脲酶。构效关系（SAR）表明，含有2,5 - 二氯和2 - 氯部分的呋喃查尔酮衍生物可被视为脲酶抑制的潜在先导试剂。计算机分子对接研究结果与实验生物学发现一致。本研究结果可能有助于未来从这类具有生物活性的呋喃查尔酮中发现和设计新型高效脲酶抑制剂药物。
