Activity of 1-aryl-4-(naphthalimidoalkyl) piperazine derivatives against Leishmania major and Leishmania mexicana |
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| Institution: | 1. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry and University Hospital, Palacky University Olomouc, Czech Republic;2. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden;3. A.V. Bogatsky Physico-Chemical Institute of National Academy of Sciences of Ukraine, Odessa, Ukraine;4. I.I. Mechnikova Odessa National University, Odessa, Ukraine;1. Institute of Pharmacy, Department of Pharmaceutical Biology, University of Greifswald, 17491 Greifswald, Germany;2. School of Pharmacy, College of Health Sciences, Addis Ababa University, Churchill Street, 1176 Addis Ababa, Ethiopia;3. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, 160062 Mohali, India;1. Biosecurity SA, Adelaide, SA 5001, Australia;2. School of Animal and Veterinary Sciences, The University of Adelaide, SA 5005, Australia;3. School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, SA 5001, Australia;4. 22 Trevor Terrace Blackwood, SA 5051, Australia;5. Istituto Zooprofilattico Sperimentale della Lombardia e dell''Emilia Romagna and OIE Reference Laboratory for Rabbit Haemorrhagic Disease and for Myxomatosis, Via Bianchi 7/9, 25124 Brescia, Italy;6. Institute for Applied Ecology, University of Canberra, Bruce, ACT 2617, Australia;7. Australian National Wildlife Collection, National Research Collections CSIRO, Crace, ACT 2911, Australia;8. CSIRO Health & Biosecurity, Acton, ACT 2601, Australia;9. Invasive Species and Environment Biosecurity, Department of Primary Industries and Regional Development, Albany, WA 6330, Australia;10. Biosecurity Tasmania, Newtown, Tasmania 7008, Australia;11. NSW Department of Primary Industries, Orange, NSW 2800, Australia;12. Centre for Invasive Species Solutions, Bruce, ACT 2617, Australia;1. Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510542, China;2. Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt |
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| Abstract: | A series of 1-aryl-4-(phthalimidoalkyl) piperazines and 1-aryl-4-(naphthalimidoalkyl) piperazines were retrieved from a proprietary library based on their high structural similarity to haloperidol, an antipsychotic with antiparasitic activity, and assessed as potential antileishmanial scaffolds. Selected compounds were tested for antileishmanial activity against promastigotes of Leishmania major and Leishmania mexicana in dose-response assays. Two of the 1-aryl-4-(naphthalimidoalkyl) piperazines (compounds 10 and 11) were active against promastigotes of both Leishmania species without being toxic to human fibroblasts. Their activity was found to correlate with the length of their alkyl chains. Further analyses showed that compound 11 was also active against intracellular amastigotes of both Leishmania species. In promastigotes of both Leishmania species, compound 11 induced collapse of the mitochondrial electrochemical potential and increased the intracellular Ca2+ concentration. Therefore, it may serve as a promising lead compound for the development of novel antiparasitic drugs. |
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