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Synthesis and characterization of pyrrolo[1,2-a]quinoline derivatives for their larvicidal activity against Anopheles arabiensis

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Abstract

Certain tetrahydropyrido[1,2-a]quinolines and pyrroloquinoline homologs have shown various biological activities such as antimicrobials, crop-protectings, diuretics, antioxidants, anticoagulants, and antimalarial activities. Keeping this observation in mind, we envisaged to synthesize and characterize a series of novel ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-3-carboxylates and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-2,3-dicarboxylates (2a-k). Quaternary salts of lepidine such as 1-[2-(substituted phenyl)-2-oxoethyl]-4-methylquinolin-1-ium bromide (1a-f) were obtained by stirring lepidine with different phenacyl bromides in acetone at room temperature separately. These quaternary salts of lepidine (1a-f) were then treated with electron-deficient ethyl propiolate and dimethyl-but-2-yne-dioate separately, in the presence of anhydrous K2CO3 and dimethylformamide (DMF) solvent to obtain ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-3-carboxylates and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-2,3-dicarboxylates, respectively (2a-k). The newly synthesized compounds were assessed by spectroscopic techniques to determine their structures. Based on our previous study on the similar pharmacophore, the synthesized compounds 2a-k were screened for their larvicidal activity against Anopheles arabiensis using a standard World Health Organization larvicidal assay; compounds 2b and 2e at 8.12 and 9.2 μM exhibited the highest larval mortality at 78 and 89%, respectively, when compared with the negative control acetone, and it demonstrated less activity, which was similar to the positive control, temephos. Finally, the test compound 2e at 9.2 μM, resulted in an 89% mortality rate after 48 h of exposure, followed by compound 2b at 8.12 μM with a 78% mortality rate. Compounds 2f, 2d, and 2c showed intermediate toxicity, and the mortality rate was lower than 60% for larvae exposed to any of the remaining test compounds.

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Acknowledgements

The authors are thankful to the Department of Chemistry, Rani Channamma University, Belagavi, for providing the facilities. We are also thankful to the Medical Research Council for its facilities to screen the compounds for larvicidal activity. The authors are grateful to the National Research Foundation, South Africa and the Durban University of Technology for support and encouragement. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Chemistry, School of Basic Science, Rani Channamma University, Belagavi, 591156, India

    Vijayakumar Uppar & Basavaraj Padmashali

  2. Institute for Stem Cell Biology and Regeneration Medicine, NCBS, TIFR GKVK Campus Bellary Road, Bangalore, 560065, India

    Sandeep Chandrashekharappa & Mahendra K. Mohan

  3. Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, 31982, Kingdom of Saudi Arabia

    Katharigatta N. Venugopala

  4. Department of Biotechnology and Food Technology, Faculty of Applied Sciences, Durban University of Technology, Durban, 4001, South Africa

    Katharigatta N. Venugopala & Bharti Odhav

  5. Faculty of Pharmacy, Philadelphia University, PO Box (1), Amman, 19392, Jordan

    Pran Kishore Deb

  6. Interdisciplinary Center for Nanotoxicity, Department of Chemistry, Physics and Atmospheric Sciences, Jackson State University, Jackson, MS, 39217, USA

    Supratik Kar

  7. Department of Pharmaceutical Sciences, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia

    Osama I. Alwassil

  8. CREAN-IMBIV (CONICET-UNC), Av. Valparaíso s.n., Córdoba, Argentina

    Raquel M. Gleiser

  9. FCEFyN, Universidad Nacional de Cordoba, AV. Sarsfield 299, 5000, Cordoba, Argentina

    Raquel M. Gleiser

  10. Instituto de Investigaciones Biológicas y Tecnilógicas (IIByT-CONICET), Cátedra de Quimica Biológica, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Córdoba, Argentina

    Daniel Garcia

  11. Department of Public Health Medicine, Howard College Campus, University of KwaZulu-Natal, Durban, 4001, South Africa

    Rashmi Venugopala

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  1. Vijayakumar Uppar
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  2. Sandeep Chandrashekharappa
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  3. Katharigatta N. Venugopala
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  11. Rashmi Venugopala
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Correspondence to Katharigatta N. Venugopala or Basavaraj Padmashali.

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Uppar, V., Chandrashekharappa, S., Venugopala, K.N. et al. Synthesis and characterization of pyrrolo[1,2-a]quinoline derivatives for their larvicidal activity against Anopheles arabiensis. Struct Chem 31, 1533–1543 (2020). https://doi.org/10.1007/s11224-020-01516-w

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