Kumar Arvind, Agarwal Drishti, Sharma Bhawana, Gupta Rinkoo Devi, Awasthi Satish Kumar
Chemical Biology Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India.
Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi 110021, India.
ACS Omega. 2024 Jul 12;9(29):31611-31619. doi: 10.1021/acsomega.4c01628. eCollection 2024 Jul 23.
Molybdenum trioxide has been proven to be an efficient catalyst in synthesizing mixed -benzoyl piperidine dispiro-1,2,4,5-tetraoxane analogues using a one-pot reaction. This catalyst facilitated the synthesis of 21 tetraoxanes using cyclic, acyclic, and aromatic ketones. The structure and methodology of this reaction have been validated by single-crystal X-ray analysis of compound ″3g″. The nature of dispiro-1,2,4,5-tetraoxane being synthesized has an impact on the overall yield of tetraoxanes such as symmetric dispiro-1,2,4,5-tetraoxanes ranging from 53 to 82%, while yields of -benzoyl piperidine dispiro-1,2,4,5-tetraoxanes ranged from 26 to 51%. Additionally, the antiplasmodial activity of the newly developed tetraoxanes against was assessed, which exhibited significantly higher activity in the nanomolar range, with values ranging from 6.35 to 44.65 nM. Molecular docking studies revealed that newer tetraoxane derivatives bind to the active site of the falcipain-2 enzyme through H-bonding and hydrophobic contacts, which are the primary indicators of the effectiveness of the synthesized compounds. Findings suggest that these peculiar compounds may act as antiplasmodial agents, which spur further study and advancement in the battle against malaria.
三氧化钼已被证明是一种高效催化剂，可用于通过一锅法反应合成混合苯甲酰基哌啶二螺-1,2,4,5-四氧六环类似物。该催化剂利用环状、非环状和芳香族酮促进了21种四氧六环的合成。该反应的结构和方法已通过化合物“3g”的单晶X射线分析得到验证。所合成的二螺-1,2,4,5-四氧六环的性质对四氧六环的总产率有影响，例如对称二螺-1,2,4,5-四氧六环的产率为53%至82%，而苯甲酰基哌啶二螺-1,2,4,5-四氧六环的产率为26%至51%。此外，还评估了新开发的四氧六环对疟原虫的抗疟活性，其在纳摩尔范围内表现出显著更高的活性，值范围为6.35至44.65 nM。分子对接研究表明，更新的四氧六环衍生物通过氢键和疏水接触与疟原蛋白酶-2酶的活性位点结合，这是合成化合物有效性的主要指标。研究结果表明，这些特殊化合物可能作为抗疟剂，这将推动在抗击疟疾方面的进一步研究和进展。
