Diphenyleneiodonium chloride (Synonyms: DPI)

Diphenyleneiodonium (DPI) chloride (DPIC), as a NADH/NADPH oxidase inhibitor, has possessing potent antimicrobial activity against Mtb and S. aureus^[1].

In vitro efficacy test it shown that DPIC was equi-potently effective against drug-resistant clinical isolates of S. aureus with MIC of 0.5-1 mg/L as compared to S. aureus ATCC 29213. DPIC has no obvious potency against gram-negative bacteria with MIC ranging from 4-32 mg/L. DPIC also has potent antimicrobial activity against H37Rv with MIC of 0.39 µM or 0.12 mg/L^[1]. In vitro, with 0.1 mM DPIC inhibits fungal spore germination and bacterial cell proliferation^[2]. In vitro, treatment with 10 µM Diphenyleneiodonium chloride, DPI has strongest inhibition against neutrophil extracellular trap creation^[3]. In vitro test it exhibited that treatment with 0.5-4 µM DPI in HCT116 cells decrease in G1 and increase in S phase cells. In addition, DPI treatment (0.5 µM DPI for 3 days) induces senescence of MCF-7 cells^[4].

In vivo test it demonstrated that rat were administrated with 1 mg/kg DPI subcutaneously maybe protect against the functional and neurohistological damage of bupivacaine-blocked sciatic nerves in a high-fat diet/streptozotocin-induced DN model^[5]. In vivo, treatment with 5 mg/kg DPI intraperitoneally in Sprague-Dawley rats, there was obvious reduction in the intracellular ROS, the number of inflammatory cells, and cytokines (TNF-α and IL-6) in BALF compared with LPS-treated rats^[6].

References:

[1] Pandey M, et al. Diphenyleneiodonium chloride (DPIC) displays broad-spectrum bactericidal activity. Sci Rep. 2017 Sep 14;7(1):11521.

[2] Jung B, et al. Efficacy of Diphenyleneiodonium Chloride (DPIC) Against Diverse Plant Pathogens. Mycobiology. 2019 Jan 14;47(1):105-111.

[3] Ostafin M, et al. Different procedures of diphenyleneiodonium chloride addition affect neutrophil extracellular trap formation. Anal Biochem. 2016 Sep 15;509:60-66.

[4] Piszczatowska K, et al. Inhibition of NADPH Oxidases Activity by Diphenyleneiodonium Chloride as a Mechanism of Senescence Induction in Human Cancer Cells. Antioxidants (Basel). 2020 Dec 8;9(12):1248.

[5] Ji ZH, et al. Diphenyleneiodonium Mitigates Bupivacaine-Induced Sciatic Nerve Damage in a Diabetic Neuropathy Rat Model by Attenuating Oxidative Stress. Anesth Analg. 2017 Aug;125(2):653-661.

[6] Kim SK, et al. Protective effects of diphenyleneiodonium, an NADPH oxidase inhibitor, on lipopolysaccharide-induced acute lung injury. Clin Exp Pharmacol Physiol. 2019 Feb;46(2):153-162.