On the mechanism of action of the fungicide chloroneb

Chloroneb (1,4-dichloro-2,5-dimethoxybenzene) is a fungicide with moderate systemic properties and selective activity toward certain fungi (e.g., Phytophthora, Pythium, Botrytis, Mucor). Although the compound is metabolized by some fungi to the toxic oxidation products DCMP (2,5-dichloro-4-methoxyphenol) and DCHQ (2,5-dichlorohydroquinone) the fungitoxic principle is chloroneb per se. It causes a lysis of the inner mitochondrial membrane of sensitive fungi, attacks the nuclear membrane and also other membranes at higher doses. Oxygen consumption by isolated mitochondria slowly decreases, but the respiratory control quotient remains nearly constant. No specific uncoupling activity or inhibition of the respiratory chain could be detected. Chloroneb is bound to the mitochondrial membrane in sensitive organisms, and a good correlation exists between binding capacity, damage to mitochondrial structure and function, and growth inhibitory effects. DCMP has a nearly identical effect, but some additional uncoupling activity whereas DCHQ is different in its mechanism of action. A comparison of a chloroneb-sensitive strain of Mucor mucedo and a resistant strain with respect to the amino acid composition of their mitochondrial membranes demonstrated a significantly diminished content of tyrosine in the resistant strain, which may be associated with the decreased binding capacity for chloroneb. Although the reason for mitochondrial destruction is not yet elucidated, counteracting effects of piperonylbutoxide and α-tocopherol acetate suggest that a radical mechanism may be involved.