Novel phthalocyanines activated by dim light for mosquito larva- and cell-inactivation with inference for their potential as broad-spectrum photodynamic insecticides

PLoS One. 2019 May 29;14(5):e0217355. doi: 10.1371/journal.pone.0217355. eCollection 2019.

Abstract

Mosquitoes are significant vectors, responsible for transmitting serious infectious diseases, including the recent epidemics of global significance caused by, for example, Zika, Dengue and Chikungunya viruses. The chemical insecticides in use for mosquito control are toxic and ineffective due to the development of resistance to them. The new approach to reduce mosquito population by releasing genetically modified males to cause female infertility is still under environmental safety evaluation. Photodynamic insecticides (PDI) have long been known as a safe and effective alternative by using dyes as the photosensitizers (PS) for activation with light to generate insecticidal singlet oxygen and reactive oxygen species. This approach warrants re-examination with advances in the chemical synthesis of novel PS, e.g. phthalocyanines (PC). Nine PC were compared with five porphyrin derivatives and two classic PS of halogenated fluoresceins, i.e. cyanosine and rose bengal experimentally for photodynamic treatment (PDT) of the larvae of laboratory-reared Aedes mosquitoes and their cell lines. Groups of 2nd instar larvae were first exposed overnight to graded concentrations of each PS in the dark followed by their exposure to dim light for up to 7 hours. Larvae of both experimental and control groups were examined hourly for viability based on their motility. Monolayers of mosquito cells were similarly PS-sensitized and exposed briefly to light at the PS-specific excitation wavelengths. Cell viability was assessed by MTT reduction assays. Of the 16 PS examined for photodynamic inactivation of the mosquito larvae, effective are three novel PC, i.e. amino-Si-PC1 and -PC2, anilinium Zn-PC3.4, pyridyloxy Si-PC14 and two porphyrin derivatives, i.e. TPPS2 and TMAP. Their EC50 values were determined, all falling in the nanomolar range lower than those of rose bengal and cyanosine. All PS effective in vivo were also found to dose-dependently inactivate mosquito cells photodynamically in vitro, providing cellular basis for their larvicidal activities. The present findings of novel PC with effective photodynamic larvicidal activities provide fresh impetus to the development of PDI with their established advantages in safety and efficacy. Toward that end, the insect cell lines are of value for rapid screening of new PC. The optimal excitability of PC with insect-invisible red light is inferred to have the potential to broaden the range of targetable insect pests.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aedes / drug effects
  • Animals
  • Indoles / metabolism
  • Indoles / pharmacology*
  • Insecticides / metabolism
  • Insecticides / pharmacology*
  • Isoindoles
  • Larva / drug effects
  • Mosquito Control / methods*
  • Mosquito Vectors / drug effects
  • Photosensitizing Agents / pharmacology
  • Porphyrins / pharmacology

Substances

  • Indoles
  • Insecticides
  • Isoindoles
  • Photosensitizing Agents
  • Porphyrins
  • phthalocyanine