Molecular Docking Studies and Synthesis of Amino-oxy-diarylquinoline Derivatives as Potent Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors

Simple item page
dc.contributor.authorArthit Makarasen
dc.contributor.authorMayuso Kuno
dc.contributor.authorSuwicha Patnin
dc.contributor.authorNanthawan Reukngam
dc.contributor.authorPanita Khlaychan
dc.contributor.authorSirinya Deeyohe
dc.contributor.authorPakamas Intachote
dc.contributor.authorBusakorn Saimanee
dc.contributor.authorSuchada Sengsai
dc.contributor.authorPornthip Boonsri
dc.contributor.authorApinya Chaivisuthangkura
dc.contributor.authorWandee Sirithana
dc.contributor.authorSupanna Techasakul
dc.contributor.correspondenceS. Techasakul; Department of Chemistry, Laboratory of Organic Synthesis, Chulabhorn Research Institute, Laksi, Bangkok, 10210, Thailand; email: supanna@cri.or.th
dc.date.accessioned2025-03-10T07:36:31Z
dc.date.available2025-03-10T07:36:31Z
dc.date.issued2019
dc.description.abstractIn this study, amino-oxy-diarylquinolines were designed using structure-guided molecular hybridization strategy and fusing of the pharmacophore templates of nevirapine (NVP), efavirenz (EFV), etravirine (ETV, TMC125) and rilpivirine (RPV, TMC278). The anti-HIV-1 reverse transcriptase (RT) activity was evaluated using standard ELISA method, and the cytotoxic activity was performed using MTT and XTT assays. The primary bioassay results indicated that 2-amino-4-oxy-diarylquinolines possess moderate inhibitory properties against HIV-1 RT. Molecular docking results showed that 2-amino-4-oxy-diarylquinolines 8(a-d) interacted with the Lys101 and His235 residue though hydrogen bonding and interacted with Tyr318 residue though �-� stacking in HIV-1 RT. Furthermore, 8a and 8d were the most potent anti-HIV agents among the designed and synthesized compounds, and their inhibition rates were 34.0% and 39.7% at 1 _M concentration. Interestingly, 8a was highly cytotoxicity against MOLT-3 (acute lymphoblastic leukemia), with an IC 50 of 4.63�0.62 _g/mL, which was similar with that in EFV and TMC278 (IC 50 7.76�0.37 and 1.57�0.20 _g/ml, respectively). Therefore, these analogs of the synthesized compounds can serve as excellent bases for the development of new anti-HIV-1 agents in the near future. � 2019 Georg Thieme Verlag. All rights reserved.
dc.identifier.citationDrug Research
dc.identifier.doi10.1055/a-0968-1150
dc.identifier.issn21949379
dc.identifier.scopus2-s2.0-85075814506
dc.identifier.urihttps://repository.dusit.ac.th//handle/123456789/4891
dc.languageEnglish
dc.publisherGeorg Thieme Verlag
dc.rights.holderScopus
dc.subjectanti HIV-1 activity
dc.subjecthybrid
dc.subjectmolecular docking
dc.subjectquinoline
dc.subjectsynthesis
dc.titleMolecular Docking Studies and Synthesis of Amino-oxy-diarylquinoline Derivatives as Potent Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors
dc.typeArticle
mods.location.urlhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85075814506&doi=10.1055%2fa-0968-1150&partnerID=40&md5=ff3b3822d05ec10d157aa7796904d722
oaire.citation.endPage682
oaire.citation.issue12
oaire.citation.startPage671
oaire.citation.volume69
Files
Collections
SCOPUS 2015-2019