The toxicity of angiotensin converting enzyme inhibitors to larvae of the disease vectors Aedes aegypti and Anopheles gambiae

Zatul Iffah Abu Hasan, Helen Williams, Nur M. Ismail, Hidayatul Fathi Othman, Gyles E. Cozier, K. Ravi Acharya, Elwyn R. Isaac

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The 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.

Original languageEnglish
Article number45409
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 27 Mar 2017

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disease vectors
Anopheles gambiae
peptidyl-dipeptidase A
Aedes aegypti
toxicity
instars
larvae
Culicidae
drugs
dipeptidases
peptides
larvicides
bradykinin
mosquito control
peptidases
insecticide resistance
chemical control
trypsin
insect larvae
esters

ASJC Scopus subject areas

  • General

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The toxicity of angiotensin converting enzyme inhibitors to larvae of the disease vectors Aedes aegypti and Anopheles gambiae. / Abu Hasan, Zatul Iffah; Williams, Helen; Ismail, Nur M.; Othman, Hidayatul Fathi; Cozier, Gyles E.; Acharya, K. Ravi; Isaac, Elwyn R.

In: Scientific Reports, Vol. 7, 45409, 27.03.2017.

Research output: Contribution to journalArticle

Abu Hasan, Zatul Iffah ; Williams, Helen ; Ismail, Nur M. ; Othman, Hidayatul Fathi ; Cozier, Gyles E. ; Acharya, K. Ravi ; Isaac, Elwyn R. / The toxicity of angiotensin converting enzyme inhibitors to larvae of the disease vectors Aedes aegypti and Anopheles gambiae. In: Scientific Reports. 2017 ; Vol. 7.
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