Nafie Mohamed S, Awad Noha M, Tag Hend M, Abd El-Salam Ibrahim M, Diab Mohamed K, El-Shatoury Sahar A
Chemistry Department, Faculty of Science, Suez Canal University, Ismailia, 41522, Egypt.
Department of Botany and Microbiology, Faculty of Science, Suez Canal University, Ismailia, 41522, Egypt.
Appl Microbiol Biotechnol. 2021 Mar;105(6):2427-2439. doi: 10.1007/s00253-021-11177-2. Epub 2021 Feb 24.
The development of new anticancer agents with a selective action mechanism has become a significant scientific challenge, especially as cancers remain the world's leading cause of death. Actinobacteria and its bioactive compounds have recently become a promising perspective alternative to cancer therapy. In this study, some extracted metabolites of Micromonospora exhibited potent antimicrobial with microbial inhibition zone ≥ 7 mm, and cytotoxic activities against MCF-7 and HepG2 cell lines with promising activities ≥ 85%. Additionally, treatment of DENA/CCl4 rats with the strain Micromonospora sp1 has induced a substantial amelioration of the liver functions, enhancing liver architecture near normal and antioxidant properties through elevation of antioxidant enzyme levels. So that these preliminary results can provide metabolites from Micromonospora sp1 as an anti-liver cancer therapy. Finally, we introduced the chemical profiling of Micromonospora sp1 metabolic extract by LC-QTOF-MS-MS technique, where eight compounds with reported antioxidant property anti-liver cancer activity were targeted, validated as iNOS inhibitor through molecular docking studies. The findings in this study can be a significant step towards studying natural bioactive products produced by Micromonospora spp. as agents for anti-liver cancer. KEY POINTS: • Metabolites of Micromonospora strain from unexploited Egyptian habitats were investigated with LC/MS library-based chemical profile and molecular docking studies as iNOS inhibitors. • Some Micromonospora strains exhibited potent antimicrobial with microbial inhibition zone ≥ 7 mm, and cytotoxic activities against MCF-7 and HepG2 cell lines with promising activities ≥ 85%. • Micromonospora extract exhibited anti-liver cancer activity in vivo through the antioxidant property by inhibiting the liver cancer biomarkers (LDH and AFP) and enhancing other biochemical parameters.
开发具有选择性作用机制的新型抗癌药物已成为一项重大的科学挑战，尤其是癌症仍是全球主要死因的情况下。放线菌及其生物活性化合物最近已成为癌症治疗中一个有前景的替代选择。在本研究中，小单孢菌的一些提取代谢产物表现出强效抗菌活性，抑菌圈≥7毫米，并且对MCF-7和HepG2细胞系具有细胞毒性活性，活性有望达到≥85%。此外，用小单孢菌sp1菌株处理DENA/CCl_{4}大鼠可显著改善肝功能，通过提高抗氧化酶水平使肝脏结构接近正常并增强抗氧化特性。因此，这些初步结果可为小单孢菌sp1的代谢产物作为抗肝癌治疗提供依据。最后，我们通过LC-QTOF-MS-MS技术介绍了小单孢菌sp1代谢提取物的化学图谱分析，其中针对八种具有报道的抗氧化特性和抗肝癌活性的化合物，通过分子对接研究验证其为诱导型一氧化氮合酶（iNOS）抑制剂。本研究中的发现可能是朝着研究小单孢菌属产生的天然生物活性产物作为抗肝癌药物迈出的重要一步。要点：• 利用基于LC/MS库的化学图谱分析和分子对接研究，将未开发的埃及栖息地的小单孢菌菌株代谢产物作为iNOS抑制剂进行研究。• 一些小单孢菌菌株表现出强效抗菌活性，抑菌圈≥7毫米，并且对MCF-7和HepG2细胞系具有细胞毒性活性，活性有望达到≥85%。• 小单孢菌提取物通过抑制肝癌生物标志物（乳酸脱氢酶和甲胎蛋白）并增强其他生化参数，在体内通过抗氧化特性表现出抗肝癌活性。
