Vimal Archana, Siddiqui Mohammad Haris, Verma Ashish, Kumar Awanish
Department of Bioengineering, Integral University, Lucknow, India.
Department of Biotechnology, National Institute of Technology, Raipur, India.
J Complement Integr Med. 2021 Dec 3;20(2):413-424. doi: 10.1515/jcim-2021-0172. eCollection 2023 Jun 1.
is a pathogen responsible for causing a wide range of infectious diseases. The emergence of multi-drug resistance (MDR) in this microbe is a big challenge. L-asparaginase (less explored drug target) is selected as a drug target because it is actively involved in the virulence mechanism. To block this virulent enzyme, curcumin that is traditionally renowned for its medicinal properties was examined. However, its pharmacological behavior and targeting property is less understood because of its poor bioavailability. Therefore, the present work explores the antimicrobial effect of both curcumin and its degradation product against the MDR pathogen.
Molecular docking studies were carried out to evaluate the inhibitory effect of curcumin and its degradation product against the L-asparaginase enzyme using Schrodinger Maestro interface tools. The Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) profile of all the test ligands was also performed.
The docking score of curcumin was -5.465 kcal/mol while its degradation product curcumin glucuronide has the lowest i.e., -6.240 kcal/mol. All the test ligands showed better or comparable docking scores with respect to control (Ciprofloxacin). Arg 142 and Asn 84 amino acid residues of L-asparaginase were found to be interacting with test ligands inside the binding pocket of the target protein. ADME/toxicology study also indicated the potency of curcumin/curcumin degradation products as a potent inhibitor.
It was found that both curcumin and its degradation products have the potential to inhibit . This information could be valuable for futuristic drug candidate development against this pathogen and could be a potential lead for mitigation of MDR.
是一种可导致多种传染病的病原体。这种微生物中多重耐药性（MDR）的出现是一个巨大挑战。L-天冬酰胺酶（研究较少的药物靶点）被选为药物靶点，因为它积极参与毒力机制。为了阻断这种毒性酶，研究了传统上因其药用特性而闻名的姜黄素。然而，由于其生物利用度差，其药理行为和靶向特性了解较少。因此，本研究探讨了姜黄素及其降解产物对多重耐药病原体的抗菌作用。
使用薛定谔大师界面工具进行分子对接研究，以评估姜黄素及其降解产物对L-天冬酰胺酶的抑制作用。还对所有测试配体的吸收、分布、代谢、排泄和毒性（ADMET）特征进行了研究。
姜黄素的对接分数为-5.465千卡/摩尔，而其降解产物姜黄素葡萄糖醛酸苷的对接分数最低，即-6.240千卡/摩尔。所有测试配体相对于对照（环丙沙星）均显示出更好或相当的对接分数。发现L-天冬酰胺酶的Arg 142和Asn 84氨基酸残基与目标蛋白结合口袋内的测试配体相互作用。ADME/毒理学研究也表明姜黄素/姜黄素降解产物作为有效抑制剂的潜力。
发现姜黄素及其降解产物均有抑制的潜力。这一信息对于未来针对该病原体的候选药物开发可能具有重要价值，并且可能是缓解多重耐药性的潜在线索。
