Validamycin A

Validamycin A is an agricultural antibiotic fungicide that protects crops from the fungus Rhizoctonia solani by inhibiting trehalase, with an IC₅₀ value of 72μM^[1]. Validamycin A also inhibits the growth of Aspergillus flavus (MIC value: 1μg/mL) and is commonly used for controlling diseases such as rice sheath blight and potato black scurf, as well as for studying trehalase activity and trehalose synthesis in biological systems^[2,3,4,5].

In vitro, Validamycin A (0.125-1μg/mL), either alone or in combination with amphotericin B (2μg/mL), treatment of human bronchial epithelial cells (BEAS-2B) for 24h did not induce significant cytotoxicity. Validamycin A (1μg/mL) treatment of the Aspergillus flavus ATCC 204304 strain for 24h significantly reduced the adhesion capacity of A. flavus^[1]. Validamycin A (1μM) treatment of Rhizoctonia cerealis shake-flask cultures for 8 days significantly reduced the total inositol content in the mycelium (by 62%) and decreased the levels of free and hydrolyzed inositol in the culture supernatant^[6].

In vivo, exposure of approximately 100 Aedes aegypti mosquito eggs to rearing medium containing Validamycin A (0.1, 0.2, 0.5mg/mL) in a 200 mL volume, with larvae continuously exposed until the adult stage, significantly delayed hatching, pupation, and eclosion processes, and dose-dependently inhibited the flight ability of adults (100% of adults were unable to fly at the 0.5mg/mL concentration)^[7]. Validamycin A (150, 300, 600, 1200mg/kg) co-administered orally with pentylenetetrazol (PTZ) to adult zebrafish, followed by 20min of electroencephalogram (EEG) recording, dose-dependently reduced the number and cumulative duration of PTZ-induced seizure-like EEG activities^[8].

References:
[1] PLABOUTONG N, EKRONARONGCHAI S, NIWETBOWORNCHAI N, et al. The inhibitory effect of validamycin A on Aspergillus flavus[J]. International Journal of Microbiology, 2020, 2020(1): 3972415.
[2] ASANO N, YAMAGUCHI T, KAMEDA Y, et al. Effect of validamycins on glycohydrolases of Rhizoctonia solani[J]. The Journal of Antibiotics, 1987, 40(4): 526-532.
[3] GARCÍA M D, ARGÜELLES J C. Trehalase inhibition by validamycin A may be a promising target to design new fungicides and insecticides[J]. Pest Management Science, 2021, 77(9): 3832-3835.
[4] HU F, SU W, LI C, et al. Control Efficacy of Validamycin A (0.2 Billion Spores/ml) Paenibacillus polymyxaDN-1 3% AS for Rice Sheath Blight[J]. Agricultural Science & Technology, 2016, 17(11): 2615.
[5] MATSUURA K. Characteristics of validamycin A in controlling Rhizoctonia diseases[M]//Natural Products. Pergamon, 1983: 301-308.
[6] ROBSON G D, KUHN P J, TRINCI A P J. Effect of validamycin A on the inositol content and branching of Rhizoctonia cerealisand other fungi[J]. Journal of General Microbiology, 1989, 135(4): 739-750.
[7] MARTEN A D, STOTHARD A I, KALERA K, et al. Validamycin A delays development and prevents flight in Aedes aegypti(Diptera: Culicidae)[J]. Journal of Medical Entomology, 2020, 57(4): 1096-1103.
[8] LEE E, BANIK A, LEE K B, et al. Assessment of the novel anti-seizure potential of validamycin A using zebrafish epilepsy model[J]. Molecules, 2024, 29(11): 2572.

Validamycin A是一种通过抑制海藻糖酶（trehalase）保护作物免受真菌Rhizoctonia solani侵害的农用抗生素类杀菌剂，IC₅₀值为72μM^[1]。Validamycin A还可抑制Aspergillus flavus生长（MIC值为1μg/mL），通常用于稻穗枯病和土豆黑斑病等病害的控制及生物体中海藻酶活性和海藻糖合成的研究^[2,3,4,5]。

在体外，Validamycin A（0.125-1μg/mL）单独或与amphotericin B（2μg/mL）联合处理人支气管上皮细胞（BEAS-2B）24h，未产生显著的细胞毒性。Validamycin A（1μg/mL）处理Aspergillus flavus ATCC 204304菌株24h，显著降低了A. flavus的附着能力^[1]。Validamycin A（1μM）处理Rhizoctonia cerealis摇瓶培养物，8天后显著降低了菌丝体中总肌醇含量（降低62%），并减少了培养上清液中游离和水解后肌醇的含量^[6]。

在体内，将约100粒埃及伊蚊卵置于含Validamycin A（0.1, 0.2, 0.5mg/mL）的200mL饲养介质中孵化，幼虫持续暴露于药物环境中直至成虫阶段，显著延迟了孵化、化蛹和羽化过程，并以剂量依赖方式抑制了成虫的飞行能力（0.5mg/mL浓度下100%的成虫无法飞行）^[7]。Validamycin A（150, 300, 600, 1200mg/kg）与pentylenetetrazol（PTZ）通过口服方式共同给予成年斑马鱼，随后进行20min的脑电图（EEG）记录，可剂量依赖性地减少PTZ诱导的癫痫样脑电活动次数和累计持续时间^[8]。