Design and antifungal evaluation of novel indole derivatives containing benzothiazole and piperidine moieties

Twenty-two indole derivatives incorporating benzothiazole and piperidine moieties were synthesized and evaluated for in vitro antifungal activity against eight phytopathogenic fungi. Most compounds exhibited significant antifungal activity, with compound H12 showing the most pronounced inhibition against Phytophthora capsici (Pc), demonstrating a median effective concentration (EC₅₀) of 8.59 μg/mL. This efficacy exceeded that of the control agents azoxystrobin (Az, EC₅₀ = 111.27 μg/mL) and fluopyram (Fl, EC₅₀ = 110.05 μg/mL), indicating superior fungicidal potency. In vivo trials on eggplant fruits revealed that H12 at 200 μg/mL provided superior protective efficacy (38.30%) against late blight compared with Az (28.72%). Mechanistic studies confirmed that H12 disrupts the cellular membrane integrity of Pc, evidenced by increased cytoplasmic leakage, higher membrane permeability, and elevated malondialdehyde levels. Furthermore, direct morphological damage was confirmed by scanning electron microscopy and fluorescence microscopy. These findings highlight H12's potential as a membrane-targeting antifungal agent, offering a novel strategy for eco-friendly pesticide development. © 2025 Society of Chemical Industry.