Identification of antimalarial leads with dual falcipain-2 and falcipain-3 inhibitory activity
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Rana, Devika | - |
dc.contributor.author | Kalamuddin, Md. | - |
dc.contributor.author | Sundriyal, Sandeep | - |
dc.contributor.author | Jaiswal, Varun | - |
dc.contributor.author | Sharma, Gaurav | - |
dc.contributor.author | Das Sarma, Koushik | - |
dc.contributor.author | Sijwali, Puran Singh | - |
dc.contributor.author | Mohmmed, Asif | - |
dc.contributor.author | Malhotra, Pawan | - |
dc.contributor.author | Mahindroo, Neeraj | - |
dc.date.available | 2020-10-20T06:42:55Z | - |
dc.date.created | 2020-08-31 | - |
dc.date.issued | 2020-01 | - |
dc.identifier.issn | 0968-0896 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/78510 | - |
dc.description.abstract | Falcipains (FPs), cysteine proteases in the malarial parasite, are emerging as the promising antimalarial drug targets. In order to identify novel FP inhibitors, we generated a pharmacophore derived from the reported co-crystal structures of inhibitors of Plasmodium falciparum Falcipain-3 to screen the ZINC library. Further, the filters were applied for dock score, drug-like characters, and clustering of similar structures. Sixteen molecules were purchased and subject to in vitro enzyme (FP-2 and FP-3) inhibition assays. Two compounds showed in vitro inhibition of FP-2 and FP-3 at low mu M concentration. The selectivity of the inhibitors can be explained based on the predicted interactions of the molecule in the active site. Further, the inhibitors were evaluated in a functional assay and were found to induce morphological changes in line with their mode of action arresting Plasmodium development. Compound 15 was most potent inhibitor identified in this study. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.relation.isPartOf | BIOORGANIC & MEDICINAL CHEMISTRY | - |
dc.title | Identification of antimalarial leads with dual falcipain-2 and falcipain-3 inhibitory activity | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000503435200023 | - |
dc.identifier.doi | 10.1016/j.bmc.2019.115155 | - |
dc.identifier.bibliographicCitation | BIOORGANIC & MEDICINAL CHEMISTRY, v.28, no.1 | - |
dc.description.isOpenAccess | N | - |
dc.citation.title | BIOORGANIC & MEDICINAL CHEMISTRY | - |
dc.citation.volume | 28 | - |
dc.citation.number | 1 | - |
dc.contributor.affiliatedAuthor | Jaiswal, Varun | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Malaria | - |
dc.subject.keywordAuthor | Cysteine proteases | - |
dc.subject.keywordAuthor | Docking | - |
dc.subject.keywordAuthor | Pharmacophore | - |
dc.subject.keywordAuthor | Falcipain-2 | - |
dc.subject.keywordAuthor | Falcipain-3 | - |
dc.subject.keywordAuthor | Antimalarials | - |
dc.subject.keywordPlus | PLASMODIUM-FALCIPARUM | - |
dc.subject.keywordPlus | CYSTEINE PROTEASE | - |
dc.subject.keywordPlus | DRUG DISCOVERY | - |
dc.subject.keywordPlus | RECOMBINANT FALCIPAIN-2 | - |
dc.subject.keywordPlus | MALARIA PARASITES | - |
dc.subject.keywordPlus | PROTEINASE | - |
dc.subject.keywordPlus | TARGETS | - |
dc.subject.keywordPlus | HEMOGLOBINASE | - |
dc.subject.keywordPlus | ZINC | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Organic | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, Republic of Korea(13120)031-750-5114
COPYRIGHT 2020 Gachon University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.