Pironetin

Pironetin is a bacterial metabolite originally isolated from Streptomyces that has diverse biological activities, including anti-proliferative, immunosuppressive, and plant growth regulatory properties.^1,2,3,4 It binds to tubulin with a K_d value of 0.33 μM and increases the critical concentration (CrC) for tubulin assembly in glycerol-assembling buffer (GAB) at a concentration of 25 μM.^2,3 It also induces G₂/M phase cell cycle arrest in 3Y1 rat fibroblasts and apoptosis in HL-60 human leukemia cells when used at concentrations of 50 ng/ml and 33 nM, respectively.^2,5 It inhibits the growth of HT-29 human colorectal and MCF-7 human breast cancer cells (IC₅₀s = 6.4 and 6 nM, respectively) but also of non-cancerous human HEK293 cells (IC₅₀ = 17 nM). It also inhibits the growth of A2780 human ovarian carcinoma cells, as well as of the drug-resistant, P-glycoprotein-expressing A2780AD subline (IC₅₀s = 8 and 25 nM, respectively). Pironetin (5 mg/kg) decreases the generation of cytotoxic T lymphocytes in mice in response to immunization by EL4 allogeneic mouse T lymphocytes.⁴ It also inhibits rice plant growth by 23% when applied nine days prior to heading.¹

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1. Kobayashi, S., Tsuchiya, K., Harada, T., et al. Pironetin, a novel plant growth regulator produced by Streptomyces sp. NK10958. I. Taxonomy, production, isolation and preliminary characterization. J. Antibiot. (Tokyo) 47(6), 697-702 (1994).

2. Kondoh, M., Usui, T., Nishikiori, T., et al. Apoptosis induction via microtubule disassembly by an antitumour compound, pironetin. Biochem. J. 340(Pt 2), 411-416 (1999).

3. Vilanova, C., Díaz-Oltra, S., Murga, J., et al. Design and synthesis of pironetin analogue/colchicine hybrids and study of their cytotoxic activity and mechanisms of interaction with tubulin. J. Med. Chem. 57(24), 10391-10403 (2014).

4. Yasui, K., Tamura, Y., Nakatani, T., et al. Chemical modification of PA-48153C, a novel immunosuppressant isolated from Streptomyces prunicolor PA-48153. J. Antibiot. (Tokyo) 49(2), 173-180 (1996).

5. Kondoh, M., Usui, T., Kobayashi, S., et al. Cell cycle arrest and antitumor activity of pironetin and its derivatives. Cancer Lett. 126(1), 29-32 (1998).