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, Hidayatulfathi, Cozier, Gyles E, Acharya, K Ravi and Isaac, R Elwyn (2017) 'The toxicity of angiotensin converting enzyme inhibitors to larvae of the disease vectors Aedes aegypti and Anopheles gambiae.'. Scientific Reports, Vol 7, p. 45409.

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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.

Item Type:	Article
Subjects:	QU Biochemistry > Enzymes > QU 135 Enzymes QU Biochemistry > Enzymes > QU 143 Enzyme inhibitors QX Parasitology > Insects. Other Parasites > QX 515 Anopheles QX Parasitology > Insects. Other Parasites > QX 525 Aedes QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1038/srep45409
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	21 Apr 2017 09:08
Last Modified:	06 Feb 2018 13:14
URI:	https://archive.lstmed.ac.uk/id/eprint/6991

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