Alkaloid-Based Insecticides as Possible Tools for Sustainable Agriculture: Mechanisms, Applications, and Challenges

Alkaloids are structurally diverse, nitrogen-containing plant secondary metabolites with well-documented insecticidal activity. This review examines alkaloid-based insecticides, focusing on their chemical diversity, biosynthetic origins, plant distribution, and physicochemical properties relevant to pest control on farms. The principal molecular targets and modes of action are discussed, including interactions with nicotinic acetylcholine receptors, acetylcholinesterase, ryanodine receptors, and GABAergic signaling. Another focus is key metabolic enzymes, together with their activity spectra against major agricultural pests. Recent advances in rational structural modification, supported by crystallographic data, computational modeling, and structure–activity relationship studies, are highlighted as strategies to enhance the potency, selectivity, and stability of these compounds. Toxicological profiles, food residue behavior, analytical challenges, and regulatory considerations are critically assessed, emphasizing that natural origin does not equate to inherent safety. The review further evaluates the role of alkaloid-based insecticides within integrated pest management systems and identifies key research gaps related to environmental safety, non-target effects, and regulatory development and harmonization. It concludes that alkaloids are positioned as potentially valuable tools for sustainable agriculture when deployed within science-based regulatory frameworks and integrated control strategies.