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Monophosphoramide derivatives: synthesis and crystal structure, theoretical and experimental studies of their biological effects

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Abstract

Synthesizing new chemical compounds and studying their biological applications have been important issues in scientific research. In this investigation, we synthesized and characterized ten new N-acetyl phosphoramidate compounds and explored the crystal structure of three others. Furthermore, not only were some kinetic inhibition parameters measured, like IC50, Ki, kp, KD for 7 compounds on human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), but also their hydrophobic parameter was determined by shake-flask technique. All compounds (number 1–10) were investigated for anti-bacterial activity against three Gram-positive and three Gram-negative bacteria, while chloramphenicol was used as a standard antibiotic. In order to find new insecticide, toxicities of 13 acephate (Ace)-derived compounds (number 20–32) were bioassayed on third larval instar of elm leaf beetle and Xanthogaleruca luteola. Additionally, screening in vivo tests revealed that two compounds had had the greatest insecticidal potential in comparison with others. It means these ones inhibited AChE (with mixed mechanisms) and general esterase more than the rest. According to ChE-QSAR models, the inhibitory potency for enzyme and bacteria is directly influenced by the electronic parameters versus structural descriptors. AChE-QSPR model of fluorescence assay indicated that the inhibitory power of AChE is primarily influenced by a set of electronic factors with the priority of: EHB > PL > δ(31P) versus structural descriptor (SA and Mv).

Graphic abstract

Synthesizing new chemical compounds and studying their biological applications have been important issues in scientific research. Toxicities of 13 acephate (Ace)-derived compounds (number 20–32) were bioassayed on third larval instar of elm leaf beetle and Xanthogaleruca luteola. Insect-QSAR equations of these compounds, based on MLR and PCA, showed that non-descriptor net charge nitrogen atom (which was affected by the polarization of N–H group) had the greatest effect on insecticidal potential.

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Acknowledgements

Financial support of this work by Iran National Science Foundation: INSF and Tarbiat Modares University, is gratefully acknowledged.

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Author notes

  1. Zahra Roshanian and Maryam Rahimzadeh Dashtaki have contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, Tarbiat Modares University, Tehran, Iran

    Khodayar Gholivand, Zahra Roshanian, Maryam Rahimzadeh Dashtaki, Zahra Hosseini, Mahboobeh Sharifi, Fahimeh Mohammadpanah, Maryam Rajabi, Mohammad Ghadamyari, Sedigheh Farshadian, Reza Hasan Sajedi, Khosro Khajeh & Neda Akbari

  2. Department of Advanced Materials, Imam Hossein University, Tehran, Iran

    Ali Asghar Ebrahimi Valmoozi

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  1. Khodayar Gholivand
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Gholivand, K., Roshanian, Z., Rahimzadeh Dashtaki, M. et al. Monophosphoramide derivatives: synthesis and crystal structure, theoretical and experimental studies of their biological effects. Mol Divers 26, 97–112 (2022). https://doi.org/10.1007/s11030-020-10160-9

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