Insect-derived Compounds as Novel Source for Drug Discovery: A Systematic Review and Critical In Silico Analysis

Natural products are remarkable sources of drug candidates due to their structural and bioactivity diversity. However, insects as an enriched global species richness remain relatively under-explored. This study evaluated the therapeutic potential of compounds derived from insects and insect-associated microbiota through a cheminformatics approach. A systematic review following PRISMA protocol was done, with literature search from three electronic databases. In silico evaluation was done to predict pharmacokinetic properties and other medicinal chemistry parameters of these compounds. A total of 357 compounds were grouped into diverse classes representing alkaloids (23.8%), polyketides (12.9%), benzenoids (11.5%), peptides (7.3%), terpenoids (5.3%), coumarins (5%), flavonoids (4.5%), quinones (3.6%), fatty acids (3.4%), and others (16.2%). Their biological activities encompassed antibacterial, antiviral, antifungal, anticancer, anti-inflammatory, antioxidant, and antidiabetic effects. Toxicity profiles were favorable, with only a small percentage showing mutagenic (19%), tumorigenic (9%), reproductive (13%), or irritant (16%) properties. In addition, out of the 167 compounds subjected to toxicity prediction, 58 exhibited no toxic effect. The compounds also demonstrated favorable oral bioavailability and a high gastrointestinal absorption rate of about 71%. Principal component analysis revealed significant similarity in physicochemical properties with FDA-approved drugs. In general, the compounds present a strong potential for development into orally administered drugs.