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

• Published in: Structural chemistry 2020-08, Vol.31 (4), p.1533-1543
• Main Authors: Uppar, Vijayakumar, Chandrashekharappa, Sandeep, Venugopala, Katharigatta N., Deb, Pran Kishore, Kar, Supratik, Alwassil, Osama I., Gleiser, Raquel M., Garcia, Daniel, Odhav, Bharti, Mohan, Mahendra K., Venugopala, Rashmi, Padmashali, Basavaraj
• Format: Article
• Language: English
• Subjects: Acetone; Anticoagulants; Antioxidants; Bromides; Carboxylates; Chemistry; Chemistry and Materials Science; Computer Applications in Chemistry; Dimethylformamide; Diuretics; Homology; Larvae; Mortality; Organic compounds; Original Research; Physical Chemistry; Potassium carbonate; Quinoline; Room temperature; Substitutes; Synthesis; Theoretical and Computational Chemistry; Toxicity
• ISSN: 1040-0400; 1572-9001
• DOI: 10.1007/s11224-020-01516-w

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 K 2 CO 3 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.