Synthesis and evaluation of 7-chloro-4-(piperazin-1-yl)quinoline-sulfonamide as hybrid antiprotozoal agents |
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| Authors: | Attar Salahuddin Afreen Inam Robyn L. van Zyl Donovan C. Heslop Chien-Teng Chen Fernando Avecilla Subhash M. Agarwal Amir Azam |
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| Affiliation: | 1. Department of Chemistry, Jamia Millia Islamia, New Delhi 110025, India;2. Pharmacology Division, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg 2193, South Africa;3. Departamento de Química Fundamental, Universidade da Coruña, Campus da Zapateira s/n, 15071 A Coruña, Spain;4. Bioinformatics Division, Institute of Cytology and Preventive Oncology (ICMR) I-7, Sector-39, Noida 201301, Uttar Pradesh, India |
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| Abstract: | A new series of 4-aminochloroquinoline based sulfonamides were synthesized and evaluated for antiamoebic and antimalarial activities. Out of the eleven compounds evaluated (F1–F11), two of them (F3 and F10) showed good activity against Entamoeba histolytica (IC50 <5 μM). Three of the compounds (F5, F7 and F8) also displayed antimalarial activity against the chloroquine-resistant (FCR-3) strain of Plasmodium falciparum with IC50 values of 2 μM. Compound F7, whose crystal structure was also determined, inhibited β-haematin formation more potently than quinine. To further understand the action of hybrid molecules F7 and F8, molecular docking was carried out against the homology model of P. falciparum enzyme dihydropteroate synthase (PfDHPS). The complexes showed that the inhibitors place themselves nicely into the active site of the enzyme and exhibit interaction energy which is in accordance with our activity profile data. Application of Lipinski ‘rule of five’ on all the compounds (F1–F11) suggested high drug likeness of F7 and F8, similar to quinine. |
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| Keywords: | Antiprotozoal agents Sulfonamides Cytotoxicity Homology modeling Docking |
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