Oligomycin A（寡霉素A，AbMole，M1997）是一種大環(huán)內(nèi)酯類抗生素，也是線粒體ATP合成酶（F1Fo ATPase）的強(qiáng)效抑制劑。它通過不可逆地結(jié)合F1Fo ATP酶的F0亞基，阻斷ATP合成，導(dǎo)致細(xì)胞能量代謝崩潰。近年來，Oligomycin A在抗腫瘤和抗真菌領(lǐng)域受到廣泛關(guān)注[1]。Oligomycin A（寡霉素A，CAS No.：579-13-5）在 K562（慢性髓系白血病）的IC50為1.52±0.13 nM，并對多藥耐藥亞系K562/4也表現(xiàn)出抑制活性[2]。Oligomycin A對MCF-7（乳腺癌）的抑制活性也比較強(qiáng)，IC50為1.76 ± 0.24 nM[3, 4]，當(dāng)與糖酵解抑制劑（如2-脫氧葡萄糖）聯(lián)用可顯著增強(qiáng)抗增殖效果[4]。Oligomycin A（MCH 32）在小鼠異種移植瘤（肝癌）中顯著抑制SALL4 SNU-398和HCC26.1腫瘤生長，且未對小鼠體重造成明顯影響[5]。Oligomycin A還常用于研究細(xì)胞的線粒體，例如Oligomycin A可在1 μM的濃度下抑制成纖維細(xì)胞的氧化磷酸化，以探究細(xì)胞供能與衰老之間的關(guān)聯(lián)[6]。Oligomycin A還可以低劑量（0.5 mg/kg）保護(hù)雄性大鼠免受缺血性急性腎損傷[7]。Oligomycin A（1 mg/kg，腹腔注射）有效抑制了小鼠的ATP合成，在上述實驗中Oligomycin A溶于5%的乙醇：95%的生理鹽水[8]。 Oligomycin A對多種植物病原真菌，如稻瘟病菌(Pyricularia oryzae)、小麥赤霉病菌(Magnaporthe oryzae Triticum)和鐮刀菌(Fusarium spp.)均表現(xiàn)出顯著抑制效果，其機(jī)理涉及菌絲生長、孢子萌發(fā)、芽管伸長和孢子形成等環(huán)節(jié)的抑制[9]。
 
范例詳解
Mitochondrion. 2024 May;76:101856.   
參考文獻(xiàn)
[1] Nafie, M. S.; Alshams, M. A.; Diab, M. K.; et al. Beyond ATP Synthase Inhibition: Chemical Diversification, Bioactivities, and Therapeutic Potential of Oligomycin A. Chemical biology & drug design 2025, 106 (4), e70173.
[2] Lysenkova, L. N.; Saveljev, O. Y.; Omelchuk, O. A.; et al. Synthesis, antimicrobial and antiproliferative properties of epi-oligomycin A, the (33S)-diastereomer of oligomycin A. Natural product research 2020, 34 (21), 3073-3081.
[3] Omelchuk, O. A.; Malyshev, V. I.; Medvedev, M. G.; et al. Stereochemistries and Biological Properties of Oligomycin A Diels-Alder Adducts. The Journal of organic chemistry 2021, 86 (12), 7975-7986.
[4] Scherbakov, A. M.; Sorokin, D. V.; Omelchuk, O. A.; et al. Glucose starvation greatly enhances antiproliferative and antiestrogenic potency of oligomycin A in MCF-7 breast cancer cells. Biochimie 2021, 186, 51-58.
[5] Tan, J. L.; Li, F.; Yeo, J. Z.; et al. New High-Throughput Screening Identifies Compounds That Reduce Viability Specifically in Liver Cancer Cells That Express High Levels of SALL4 by Inhibiting Oxidative Phosphorylation. Gastroenterology 2019, 157 (6), 1615-1629.e1617.
[6] Lin, Y. H.; Lin, K. L.; Wang, X. W.; et al. Miro1 improves the exogenous engraftment efficiency and therapeutic potential of mitochondria transfer using Wharton's jelly mesenchymal stem cells. Mitochondrion 2024, 76, 101856.
[7] Tanaka, R.; Takayama, J.; Takaoka, M.; et al. Retraction: Oligomycin, an F1FO-ATPase Inhibitor, Protects Against Ischemic Acute Kidney Injury in Male but Not in Female Rats. 2013, 123 (3), 227-234.
[8] Brum, E. d. S.; Fialho, M. F. P.; Fischer, S. P. M.; et al. Relevance of mitochondrial dysfunction in the reserpine-induced experimental fibromyalgia model. 2020, 57 (10), 4202-4217.
[9] Yamamoto, K.; Futamura, Y.; Uson-Lopez, R. A.; et al. YO-001A, a new antifungal agent produced by Streptomyces sp. YO15-A001. The Journal of antibiotics 2019, 72 (12), 986-990.