Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae
Balamuthia mandrillaris and Naegleria fowleri are opportunistic protozoan pathogens capable of producing infection of the central nervous system with more than 95% mortality rate. Previously, we have synthesized several compounds with antiamoebic properties; however, synthesis of compounds that are...
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2020
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| Online Access: | http://hdl.handle.net/11073/21417 |
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| _version_ | 1864513444184588289 |
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| author | Anwar, Ayaz |
| author2 | Mungroo, Mohammad Ridwane Khan, Simal Fatima, Itrat Rafique, Rafaila Khan, Khalid Mohammed Siddiqui, Ruqaiyyah Khan, Naveed |
| author2_role | author author author author author author author |
| author_facet | Anwar, Ayaz Mungroo, Mohammad Ridwane Khan, Simal Fatima, Itrat Rafique, Rafaila Khan, Khalid Mohammed Siddiqui, Ruqaiyyah Khan, Naveed |
| author_role | author |
| dc.creator.none.fl_str_mv | Anwar, Ayaz Mungroo, Mohammad Ridwane Khan, Simal Fatima, Itrat Rafique, Rafaila Khan, Khalid Mohammed Siddiqui, Ruqaiyyah Khan, Naveed |
| dc.date.none.fl_str_mv | 2020 2021-04-15T10:13:43Z 2021-04-15T10:13:43Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | Anwar, A.; Mungroo, M.R.; Khan, S.; Fatima, I.; Rafique, R.; Kanwal; Khan, K.M.; Siddiqui, R.; Khan, N.A. Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae. Antibiotics 2020, 9, 188. https://doi.org/10.3390/antibiotics9040188 2079-6382 http://hdl.handle.net/11073/21417 10.3390/antibiotics9040188 |
| dc.language.none.fl_str_mv | en_US |
| dc.publisher.none.fl_str_mv | MDPI |
| dc.relation.none.fl_str_mv | https://doi.org/10.3390/antibiotics9040188 |
| dc.subject.none.fl_str_mv | Brain-eating amoeba Naegleria Balamuthia Azole Synthesis Nanoparticles |
| dc.title.none.fl_str_mv | Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae |
| dc.type.none.fl_str_mv | Peer-Reviewed Published version info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Balamuthia mandrillaris and Naegleria fowleri are opportunistic protozoan pathogens capable of producing infection of the central nervous system with more than 95% mortality rate. Previously, we have synthesized several compounds with antiamoebic properties; however, synthesis of compounds that are analogues of clinically used drugs is a highly desirable approach that can lead to effective drug development against these devastating infections. In this regard, compounds belonging to the azole class possess wide range of antimicrobial properties and used clinically. In this study, six novel benzimidazole, indazole, and tetrazole derivatives were synthesized and tested against brain-eating amoebae. These compounds were tested for their amoebicidal and static properties against N. fowleri and B. mandrillaris. Furthermore, the compounds were conjugated with silver nanoparticles and characterized. The synthetic heterocyclic compounds showed up to 72% and 65% amoebicidal activities against N. fowleri and B. mandrillaris respectively, while expressing up to 75% and 70% amoebistatic activities, respectively. Following conjugation with silver nanoparticles, amoebicidal activities of the drugs increased by up to 46 and 36% versus B. mandrillaris and N. fowleri. Minimal effects were observed when the compounds were evaluated against human cells using cytotoxicity assays. In summary, azole compounds exhibited potent activity against N. fowleri and B. mandrillaris. Moreover, conjugation of the azole compounds with silver nanoparticles further augmented the capabilities of the compounds against amoebae. |
| format | article |
| id | aus_d2f14fa0d663e5009e6edee45893c878 |
| identifier_str_mv | Anwar, A.; Mungroo, M.R.; Khan, S.; Fatima, I.; Rafique, R.; Kanwal; Khan, K.M.; Siddiqui, R.; Khan, N.A. Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae. Antibiotics 2020, 9, 188. https://doi.org/10.3390/antibiotics9040188 2079-6382 10.3390/antibiotics9040188 |
| language_invalid_str_mv | en_US |
| network_acronym_str | aus |
| network_name_str | aus |
| oai_identifier_str | oai:repository.aus.edu:11073/21417 |
| publishDate | 2020 |
| publisher.none.fl_str_mv | MDPI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Novel Azoles as Antiparasitic Remedies against Brain-Eating AmoebaeAnwar, AyazMungroo, Mohammad RidwaneKhan, SimalFatima, ItratRafique, RafailaKhan, Khalid MohammedSiddiqui, RuqaiyyahKhan, NaveedBrain-eating amoebaNaegleriaBalamuthiaAzoleSynthesisNanoparticlesBalamuthia mandrillaris and Naegleria fowleri are opportunistic protozoan pathogens capable of producing infection of the central nervous system with more than 95% mortality rate. Previously, we have synthesized several compounds with antiamoebic properties; however, synthesis of compounds that are analogues of clinically used drugs is a highly desirable approach that can lead to effective drug development against these devastating infections. In this regard, compounds belonging to the azole class possess wide range of antimicrobial properties and used clinically. In this study, six novel benzimidazole, indazole, and tetrazole derivatives were synthesized and tested against brain-eating amoebae. These compounds were tested for their amoebicidal and static properties against N. fowleri and B. mandrillaris. Furthermore, the compounds were conjugated with silver nanoparticles and characterized. The synthetic heterocyclic compounds showed up to 72% and 65% amoebicidal activities against N. fowleri and B. mandrillaris respectively, while expressing up to 75% and 70% amoebistatic activities, respectively. Following conjugation with silver nanoparticles, amoebicidal activities of the drugs increased by up to 46 and 36% versus B. mandrillaris and N. fowleri. Minimal effects were observed when the compounds were evaluated against human cells using cytotoxicity assays. In summary, azole compounds exhibited potent activity against N. fowleri and B. mandrillaris. Moreover, conjugation of the azole compounds with silver nanoparticles further augmented the capabilities of the compounds against amoebae.Sunway UniversityPakistan Academy of SciencesMDPI2021-04-15T10:13:43Z2021-04-15T10:13:43Z2020Peer-ReviewedPublished versioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfAnwar, A.; Mungroo, M.R.; Khan, S.; Fatima, I.; Rafique, R.; Kanwal; Khan, K.M.; Siddiqui, R.; Khan, N.A. Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae. Antibiotics 2020, 9, 188. https://doi.org/10.3390/antibiotics90401882079-6382http://hdl.handle.net/11073/2141710.3390/antibiotics9040188en_UShttps://doi.org/10.3390/antibiotics9040188oai:repository.aus.edu:11073/214172024-08-22T12:00:30Z |
| spellingShingle | Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae Anwar, Ayaz Brain-eating amoeba Naegleria Balamuthia Azole Synthesis Nanoparticles |
| status_str | publishedVersion |
| title | Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae |
| title_full | Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae |
| title_fullStr | Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae |
| title_full_unstemmed | Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae |
| title_short | Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae |
| title_sort | Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae |
| topic | Brain-eating amoeba Naegleria Balamuthia Azole Synthesis Nanoparticles |
| url | http://hdl.handle.net/11073/21417 |