Synthesis, <i>In Vitro</i> Activity, and Molecular Docking of 1,5-Disubstituted Tetrazol-1,2,3-triazole Hybrids against Fungal Plant Pathogen <i>Botrytis cinerea</i> and <i>Colletotrichum gloeosporioides</i>

Fungal resistance to commercial fungicides poses a serious threat to global food security. In this work, a series of 24 novel 1,5-disubstituted tetrazole-1,2,3-triazole hybrids was synthesized under mild reaction conditions without the need for purification by column chromatography through a two-step, four-process sequence involving S_<i>N</i>2 substitution, CuAAC, oxidation, and the Ugi-azide multicomponent reaction, using propargyl alcohol as a key bifunctional starting reagent. The antifungal activity of the synthesized compounds was evaluated <i>in vitro</i> against <i>Botrytis cinerea</i> and <i>Colletotrichum gloeosporioides</i>. The compound derived from phenylamino-pyrimidine exhibited excellent activity, with 100% and up to 55% inhibition against <i>B. cinerea</i> and <i>C. gloeosporioides</i>, respectively. Molecular docking studies revealed that this compound interacts favorably with the active sites of CYP51 and CYP51B enzymes, establishing π-π stacking, hydrophobic interactions, and coordination with the heme group, supporting its observed bioactivity. These findings highlight the potential of this hybrid scaffold as a promising lead for agrochemical fungicide development. Notably, this is the first application of a 1,5-disubstituted tetrazole synthesized via the Ugi-azide MCR in agrochemistry, broadening the scope of this powerful synthetic tool beyond medicinal chemistry.