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.