Abu Hasan Z.-I.Williams H.Ismail N.M.Othman H.Cozier G.E.Acharya K.R.Isaac E.R.2024-05-282024-05-2820172045232210.1038/srep454092-s2.0-85016285336https://www.scopus.com/inward/record.uri?eid=2-s2.0-85016285336&doi=10.1038%2fsrep45409&partnerID=40&md5=779b027b8bcfa7f51937025b54af9b7bhttps://oarep.usim.edu.my/handle/123456789/872728345667The control of mosquitoes is threatened by the appearance of insecticide resistance and therefore new control chemicals are urgently required. Here we show that inhibitors of mosquito peptidyl dipeptidase, a peptidase related to mammalian angiotensin-converting enzyme (ACE), are insecticidal to larvae of the mosquitoes, Aedes aegypti and Anopheles gambiae. ACE inhibitors (captopril, fosinopril and fosinoprilat) and two peptides (trypsin-modulating oostatic factor/TMOF and a bradykinin-potentiating peptide, BPP-12b) were all inhibitors of the larval ACE activity of both mosquitoes. Two inhibitors, captopril and fosinopril (a pro-drug ester of fosinoprilat), were tested for larvicidal activity. Within 24 h captopril had killed >90% of the early instars of both species with 3 rd instars showing greater resistance. Mortality was also high within 24 h of exposure of 1 st, 2 nd and 3 rd instars of An. gambiae to fosinopril. Fosinopril was also toxic to Ae. aegypti larvae, although the 1 st instars appeared to be less susceptible to this pro-drug even after 72 h exposure. Homology models of the larval An. gambiae ACE proteins (AnoACE2 and AnoACE3) reveal structural differences compared to human ACE, suggesting that structure-based drug design offers a fruitful approach to the development of selective inhibitors of mosquito ACE enzymes as novel larvicides. � The Author(s) 2017.en-USArticle745409