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Synthesis, Molecular Docking and Mosquitocidal Efficacy of Lawsone and its Derivatives Against the Dengue Vector Aedes aegypti L. (Diptera: Culicidae)

[ Vol. 18 , Issue. 2 ]

Author(s):

Antony Stalin*, Paul Dhivya, Ding Lin, Yue Feng, Antony Cruz Asharaja, Munusamy Rajiv Gandhi, Balakrishnan Senthamarai Kannan, Subramani Kandhasamy, Appadurai Daniel Reegan* and Yuan Chen*   Pages 170 - 180 ( 11 )

Abstract:


Background: Aedes aegypti is the primary vector of dengue, a significant public health problem in many countries. Controlling of Ae. aegypti is the biggest challenge in the mosquito control programe, and there is a need for finding bioactive molecules to control Ae. aegypti in order to prevent dengue virus transmission.

Objective: To assess the mosquitocidal property of lawsone and its 3-methyl-4H-chromen-3-yl-1- phenylbenzo[6,7]chromeno[2,3,c]pyrazole-dione derivatives (6a-6h) against various life stages of Ae. aegypti. Besides, to study the mode of action of the active compound by molecular docking and histopathological analysis.

Methods: All derivatives were synthesized from the reaction between 2-hydroxy-1,4-naphthoquinone, chromene-3-carbaldehyde, and 1-phenyl-3-methyl-pyrazol-5-one by using one pot sequential multicomponent reaction. The mosquito life stages were subjected to diverse concentrations ranging from 1.25, 2.5, 5.0, and 10 ppm for lawsone and its derivatives. The structure of all synthesized compounds was characterized by spectroscopic analysis. Docking analysis was performed using autodock tools. Midgut sections of Ae. aegypti larvae were analyzed for histopathological effects.

Results: Among the nine compounds screened, derivative 6e showed the highest mortality on Ae. aegypti life stages. The analyzed LC50 and LC90 results of derivative 6e were 3.01, 5.87 ppm, and 3.41, 6.28 ppm on larvae and pupae of Ae. aegypti, respectively. In the ovicidal assay, the derivative 6e recorded 47.2% egg mortality after 96-hour post-exposure to 10 ppm concentration. In molecular docking analysis, the derivative 6e confirmed strong binding interaction (-9.09 kcal/mol and -10.17 kcal/mol) with VAL 60 and HIS 62 of acetylcholinesterase 1 (AChE1) model and LYS 255, LYS 263 of kynurenine aminotransferase of Ae. aegypti, respectively. The histopathological results showed that the derivative 6e affected the columnar epithelial cells (CC) and peritrophic membrane (pM).

Conclusion: The derivative 6e is highly effective in the life stages of Ae. aegypti mosquito and it could be used in the integrated mosquito management programe.

Keywords:

Multi-Component Reaction, 2-hydroxy-1, 4-naphthoquinone, Aedes aegypti, Mosquitocidal activity, Molecular docking.

Affiliation:

State Key Laboratory of Subtropical Silviculture, Department of Traditional Chinese Medicine, Zhejiang A&F University, Hangzhou 311300, Department of Chemistry, Nirmala College for Women, Coimbatore 641018, Tamil Nadu, State Key Laboratory of Subtropical Silviculture, Department of Traditional Chinese Medicine, Zhejiang A&F University, Hangzhou 311300, College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou3College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, P.G. and Research Department of Zoology, Pasumpon Muthuramalinga Thevar College, Melaneelithanallur 627 953, Sankarankovil, Tenkasi, Tamil Nadu, National Biodiversity Authority, 5th Floor, CSIR Road, TICEL Bio Park, Taramani, Chennai, 600113, Department of Chemistry, Tirunelveli Dakshina Mara Nadar Sangam (T D M N S) College, Valliyur, Tirunelveli 627113, Tamil Nadu, Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, National Centre for Disease Control, NTI Campus, Ballary Road, Bangalore 560003, Karnataka, State Key Laboratory of Subtropical Silviculture, Department of Traditional Chinese Medicine, Zhejiang A&F University, Hangzhou 311300



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