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Vol. 36 No. 12 (2024): Vol 36 Issue 12, 2024

Copyright (c) 2024 Jyoti Gupta, Puleng A. Thabana, Sabahat Samreen, Amir Azam, Robyn L. van Zyl, Afreen Inam

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Synthesis and Biological Evaluation of 2-(3-((2-(2-(Quinoline-4-yloxy)acetyl)-hydrazineylidene)methyl)-1H-indol-1-yl)acetamide Derivatives as Antiprotozoal Agent: In silico Molecular Docking Study

https://doi.org/10.14233/ajchem.2024.32801
Jyoti Gupta
Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India; Department of Chemistry, B.S. College, Lohardaga, Ranchi University, Ranchi, India
https://orcid.org/0009-0002-9045-1253
Puleng A. Thabana
Pharmacology Division, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg 2193, South Africa; WITS Research Institute for Malaria, Faculty of Health Sciences, University of Witwatersrand, Johannesburg 2193, South Africa
https://orcid.org/0009-0003-1092-4573
Sabahat Samreen
Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India
https://orcid.org/0009-0002-8346-9543
Amir Azam
Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India
https://orcid.org/0000-0001-7852-673X
Robyn L. van Zyl
Pharmacology Division, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg 2193, South Africa; WITS Research Institute for Malaria, Faculty of Health Sciences, University of Witwatersrand, Johannesburg 2193, South Africa
https://orcid.org/0000-0002-3778-7578
Afreen Inam
Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India
https://orcid.org/0000-0002-2783-7025

Corresponding Author(s) : Afreen Inam

ainam@jmi.ac.in

Asian Journal of Chemistry, Vol. 36 No. 12 (2024): Vol 36 Issue 12, 2024

Abstract

In an unremitting search for potential antiprotozoal agents, a series of 2-(3-((2-(2-(quinolin-4-yloxy)acetyl)hydrazineylidene)methyl)-1H-indol-1-yl)acetamide derivatives (QC1-QC11) was designed, synthesized, characterized and evaluated for its antiprotozoal activities. The anti-amoebic activity of these synthesized compounds was assessed against the HM1:IMSS strain of Entamoeba histolytica. All the compounds exhibited good to potent activity with IC50 values in the range of 0.36-30.94 µM and metronidazole (MTZ) was taken as standard (IC50 = 1.8 µM). Compound QC4 was recorded with lowest IC50 value (0.36 µM). Antimalarial screening against Plasmodium falciparum strain (NF54) revealed the poor efficacy of these compounds. Derivatives QC2 and QC4 exhibited a slight inhibitory effect on the malaria parasite compared to quinine, while showing negligible impact on red blood cell integrity. Of all the derivatives, QC4 displayed general toxicity to all the organisms and cells used in this study, with QC2 showing minimal toxicity to these biological systems. The docking study of these derivatives indicated the promising binding affinity when interacted with enzyme EhTHRase (PDB id: 3D8X). QC6 recorded with most negative binding free energy value (-8.9 kcal/mol) showing strongest interaction while QC4 also had promising interaction with binding free energy -8.7 kcal/mol, hence, these derivatives are found to be promising anti-amoebic agents.

Keywords

Quinoline Indole Entamoeba histolytica Plasmodium falciparum Cytotoxicity
Gupta, J., Thabana, P. A., Samreen, S., Azam, A., van Zyl, R. L., & Inam, A. (2024). Synthesis and Biological Evaluation of 2-(3-((2-(2-(Quinoline-4-yloxy)acetyl)-hydrazineylidene)methyl)-1H-indol-1-yl)acetamide Derivatives as Antiprotozoal Agent: In silico Molecular Docking Study. Asian Journal of Chemistry, 36(12), 2911–2920. https://doi.org/10.14233/ajchem.2024.32801
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