Potent phytoregulators from Pyrenacantha volubilis targeting ERα: a promising natural alternative for breast cancer therapy.

IF 2.9 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

3 Biotech Pub Date : 2025-06-01 Epub Date: 2025-05-24 DOI:10.1007/s13205-025-04315-4

Maya Ammathil Manoharan, Senthilkumar Umapathy, Beutline Malgija

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引用次数: 0

Abstract

Selective estrogen receptor modulators (SERMs) play a vital role in ER + ve breast cancer therapy, but existing synthetic drugs have limitations. This study explores Pyrenacantha volubilis as a potential natural source for SERM using molecular docking, ADMET profiling, molecular dynamics (MD) simulations, and MM-GBSA analysis, using the Schrödinger Suite. Nine metabolites reported from the species were subjected to analysis, and all except one exhibited superior activity compared to the control. Among these, pumiloside (- 13.06 kcal/mol), strictosidine (- 11.808 kcal/mol), deoxypumiloside (- 11.686 kcal/mol), and strictosamide (- 11.479 kcal/mol) demonstrated stronger ERα binding affinities than control drugs tamoxifen and raloxifene. The receptor-ligand complexes of pumiloside and strictosidine exhibited reasonable interactions, with strictosidine showing the highest glide energy (- 52.418 kcal/mol). MD simulations and MM-GBSA analysis further confirmed the stability of these complexes under physiological conditions, with both compounds showing superior free binding energy compared to tamoxifen. Deoxypumiloside also emerged as a promising candidate with no Lipinski rule of five violations and high oral absorption, but required solubility enhancements. Additionally, 10-hydroxy camptothecin, protonated strictosidine, camptothecin, 9-methoxy camptothecin, 20-deoxy camptothecin, and 20-hexanoyl-10-methoxy camptothecin are other metabolites that exhibited good docking scores and favorable drug-like properties. These findings highlight P. volubilis as a promising SERM source, with strictosidine and pumiloside as lead candidates due to their superior receptor interactions, stability, and energetics. Further in vitro and in vivo studies are required to validate their therapeutic potential in breast cancer treatment.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04315-4.

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针对ERα的强效植物调节剂：一种有前途的乳腺癌治疗天然替代品。

选择性雌激素受体调节剂（SERMs）在ER + ve乳腺癌治疗中起着至关重要的作用，但现有的合成药物存在局限性。本研究利用Schrödinger Suite，通过分子对接、ADMET分析、分子动力学（MD）模拟和MM-GBSA分析，探讨了Pyrenacantha volubilis作为SERM的潜在天然来源。对9种代谢物进行了分析，除1种代谢物外，其余代谢物均表现出优于对照的活性。其中，pumiloside （- 13.06 kcal/mol）、strictossidine （- 11.808 kcal/mol）、脱氧pumiloside （- 11.686 kcal/mol）和strictosamide （- 11.479 kcal/mol）比对照药物他莫昔芬和雷洛昔芬表现出更强的ERα结合亲和力。槲皮苷与花螺苷的受体-配体配合物表现出合理的相互作用，其中花螺苷的滑动能最高（- 52.418 kcal/mol）。MD模拟和MM-GBSA分析进一步证实了这些配合物在生理条件下的稳定性，两种化合物均表现出优于他莫昔芬的自由结合能。脱氧苏梅苷也被认为是一种很有希望的候选药物，没有利平斯基规则的五次违反和高口服吸收，但需要提高溶解度。此外，10-羟基喜树碱、质子化伸缩桃苷、喜树碱、9-甲氧基喜树碱、20-脱氧喜树碱和20-己醇-10-甲氧基喜树碱等代谢产物也表现出良好的对接评分和良好的药物样特性。这些发现强调了卷叶假单胞菌是一种很有前途的SERM来源，由于其优越的受体相互作用、稳定性和能量学，将strictosidine和pumiloside作为主要候选者。需要进一步的体外和体内研究来验证它们在乳腺癌治疗中的治疗潜力。补充资料：在线版本包含补充资料，下载地址：10.1007/s13205-025-04315-4。

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来源期刊

3 Biotech Agricultural and Biological Sciences-Agricultural and Biological Sciences (miscellaneous)

CiteScore

6.00

自引率

0.00%

发文量

314

期刊介绍： 3 Biotech publishes the results of the latest research related to the study and application of biotechnology to: - Medicine and Biomedical Sciences - Agriculture - The Environment The focus on these three technology sectors recognizes that complete Biotechnology applications often require a combination of techniques. 3 Biotech not only presents the latest developments in biotechnology but also addresses the problems and benefits of integrating a variety of techniques for a particular application. 3 Biotech will appeal to scientists and engineers in both academia and industry focused on the safe and efficient application of Biotechnology to Medicine, Agriculture and the Environment.