Design, Synthesis, and Biological Evaluation of Novel Cyclopenta[ c ]chromene Derivatives Containing a Cinnamate Skeleton

A series of novel cyclopenta[c]chromene-cinnamate derivatives were designed via molecular hybridization of cerbinal-, chromene-, and cinnamic-acid-based scaffolds and subsequently synthesized. Their insecticidal, anti-TMV, and antifungal activities were evaluated. Most compounds showed enhanced insecticidal activity against Plutella xylostella larvae, with 4f, 4cc, and 4ll being the most potent. In anti-TMV evaluations, several compounds surpassed the efficacy of ribavirin; notably, 4s, 4f, and 4u─each outperforming the lead compound 5d─showed the highest inactivation, protection, and curative effects, respectively. Antifungal screening highlighted 4f, which achieved 100% inhibition against Phytophthora capsici (EC50 = 12.95 μg/mL). Molecular docking studies suggested that the notable anti-TMV activities of 4f and 4u were attributed to their stable interactions with the TMV coat protein. Toxicity predictions indicated that 4f has a low acute oral toxicity (category 5). With its broad-spectrum biological profile and favorable safety characteristics, compound 4f is a promising multifunctional agrochemical candidate.