Juvenile hormone mimics with phenyl ether and amide functionality to be insect growth regulators (IGRs): synthesis, characterization, computational and biological study

Abstract

A series of substituted phenyl ethers derivatives as juvenile hormone (JH) mimics (V₁-V₈) have been synthesized. Substituted phenoxyacetic acid and amino acid ethyl ester hydrochloride were prepared using NaOH, SOCl₂. DCC method has been used for amide linkage. The structure of prepared compounds has been confirmed by Fourier Transform Infra-Red (FT-IR), Electrospray ionization-Mass spectrometry (ESI-MS), Proton and Carbon-13 nuclear magnetic resonance (¹H-NMR, ¹³C-NMR) spectroscopic techniques. Biological efficacy of synthesized analogs has been carried out under laboratory conditions. Galleria mellonella (honey bee pest) has been chosen as testing insect. Juvenile hormone (JH) activity of synthesized compounds has been tested at different concentrations and compared with the standard juvenile hormone analogs (JHAs) pyriproxyfen (M₁) and fenoxycarb (M₂) against the fifth larval instar of G. mellonella. Compound ethyl 2-[2-(4-methylphenoxy)aminoacetyl]-3-phenyl-propanoate (V₆) exhibited better activity among all the synthesized compounds (V₁-V₈) with LC₅₀ and LC₉₀ values of 0.11 mg/mL and 0.56 mg/mL respectively. Compounds showed insect growth regulating (IGR) activity at lower concentrations. In silico screening of all synthesized compounds with the W-cavity of juvenile hormone-binding protein (JHBP) of insect G. mellonella has been carried out. Chemical reactivity of synthesized series has been studied using DFT/B3LYP/6-311 + G(d,2p) method. Non-toxic behavior of molecules has also been observed from ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) study using discovery studio client 3.0.

Communicated by Ramaswamy H. Sarma

Keywords:

• Juvenile hormone
• juvenile hormone analogues
• insect growth regulators
• Galleria mellonella
• lethal concentration
• juvenile hormone binding protein
• absorption, distribution, metabolism, excretion, toxicity
• density functional theory

Acknowledgements

The authors are grateful and acknowledge the Ministry of Education, Govt. of India for providing financial support. NIT Hamirpur is highly acknowledged for laboratory and other facilities. Thanks to SAIF lab, PU Chandigarh for ¹³C-NMR, ¹H-NMR, ESI-Mass (HRMS), and FT-IR spectroscopic experiments. We are also thankful to the College of Horticulture and Forestry, Neri Hamirpur (H.P.) for providing the Entomology lab facility.

Disclosure statement

The authors declare no competing interest.