Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 69, Issue 40, Pages 12039-12047Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c01642
Keywords
beta-N-acetyl-D-hexosaminidase; Of Hex1; inhibitors; molecular docking virtual screening; biphenyl-sulfonamide
Funding
- National Natural Science Foundation of China [21977035, 21837001, 21772057]
- Key Research and Development Program of Hubei Province [2020BBA052]
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The study demonstrates that compounds with a biphenyl-sulfonamide skeleton have great potential as OfHex1 inhibitors, showing higher potency than some reported nonglycosyl-based inhibitors. These compounds were found to be competitive inhibitors with respect substrate and exhibited potent drug properties, indicating their potential value in pest management.
Novel insecticidal targets are always in demand due to the development of resistance. OfHex1, a beta-N-acetyl-D-hexosaminidase identified in Ostrinia furnacalis (Asian corn borer), is involved in insect chitin catabolism and has proven an ideal target for insecticide development. In this study, structure-based virtual screening, structure simplification, and biological evaluation are used to show that compounds with a biphenyl-sulfonamide skeleton have great potential as OfHex1 inhibitors. Specifically, compounds 10k, 10u, and 10v have K-i values of 4.30, 3.72, and 4.56 mu M, respectively, and thus, they are more potent than some reported nonglycosyl-based inhibitors such as phlegmacin B-1 (K-i = 26 mu M), berberine = 12 mu M), 2 (K-i = 11.2 mu M), and 3 (K-i = 28.9 mu M). Furthermore, inhibitory kinetic assessments reveal that the target compounds are competitive inhibitors with respect substrate, and based on toxicity predictions, most of them have potent drug properties. The obtained results indicate that the biphenyl-sulfonamide skeleton characterized by simple chemical structure, synthetic tractability, potent activity, and low toxicity has potential for further development in pest management targeting OfHex1.
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