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

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