Science and Technology Production
Article
Authorship
Barick, Subrata
;
Dahiya, Sachin Dalel
;
Tiwari, Priya
;
Deb, Pran Kishore
;
Sarkar, Biprajit
;
Maity, Prasenjit
;
Rakshit, Gourav
;
Saini, Surbhi Mahender
;
Mohanlall, Viresh
;
GLEISER, RAQUEL MIRANDA
;
Venugopala, Katharigatta N.
;
Ningegowda, Raghu
;
Chandrashekharappa, Sandeep
Date
2025
Publishing House and Editing Place
ELSEVIER SCIENCE BV
Magazine
JOURNAL OF MOLECULAR STRUCTURE,
vol. 1345
ELSEVIER SCIENCE BV
Summary
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personalizedShare Link: https://authors.elsevier.com/c/1lKun54JUciCK A series of novel ethyl 3-benzoyl-7-(4-nitrobenzyl) indolizine-1-carboxylate (4a-g) and diethyl 3-(4-bromobenzoyl)-7-(4-nitrobenzyl) indolizine-1,2-dicarboxylate (4h and 4i) derivatives were synthesized and biologically assayed against Anopheles arabiensis, a malaria vector, following standard WHO larvicidal assay protocols. Among these, compounds 4c and 4e exhibited the highest potency, achieving mortality rates of 65.56 &plu...
personalizedShare Link: https://authors.elsevier.com/c/1lKun54JUciCK A series of novel ethyl 3-benzoyl-7-(4-nitrobenzyl) indolizine-1-carboxylate (4a-g) and diethyl 3-(4-bromobenzoyl)-7-(4-nitrobenzyl) indolizine-1,2-dicarboxylate (4h and 4i) derivatives were synthesized and biologically assayed against Anopheles arabiensis, a malaria vector, following standard WHO larvicidal assay protocols. Among these, compounds 4c and 4e exhibited the highest potency, achieving mortality rates of 65.56 ± 3.39 %. Although their efficacy was lower than the reference compound Temephos, these findings together with their physicochemical and pharmacokinetic profiles indicate their potential as lead candidates for more effective larvicidal agents. The structural novelty of 4c and 4e lies in the indolizine core with fluorine 4c and chlorine 4e substitutions, which differentiate them from traditional larvicidal compounds. These modifications enhance lipophilicity, potentially improving absorption and interaction with biological membranes. In silico studies were performed to understand the mechanisms of action, including molecular docking with six probable larvicidal targets. Among these, the targeted proteins 4JBV and 6ARY, revealed strong binding affinities and correlation with the larvicidal activities of our tested compounds, including the most active compounds 4c and 4e compared to Temephos. Molecular dynamics simulations validated that both compounds maintained stable complex formation, as evidenced by RMSD (<2 Å), RMSF, H-bond plots, etc. Additionally, in silico ADMET profiling assessed the pharmacokinetic properties of these compounds, revealing that 4c and 4e exhibited favorable ADME parameters (e.g. high intestinal absorption, >94 %), and acceptable toxicity levels and no Pan-Assay Interference Compounds (PAINS) alerts, indicating strong larvicidal target specificity. Their moderate synthetic accessibility (3.14 – 3.15) supports that further structural modifications could enhance their potency in anti-malarial vector agent development. Overall, the integration of promising larvicidal activity, stable target interactions, and favorable pharmacokinetics highlights the potential of 4c and 4e in the development of novel anti-malarial agents. Future studies should focus on optimizing their structural framework to enhance efficacy, providing valuable contributions to malarial vector control strategies.
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Key Words
LARVICIDALINDOLIZINEANOPHELES ARABIENSISMOLECULAR DOCKING