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

Makarasen A.; Kuno M.; Patnin S.; Reukngam N.; Khlaychan P.; Deeyohe S.; Intachote P.; Saimanee B.; Sengsai S.; Boonsri P.; Chaivisuthangkura A.; Sirithana W.; Techasakul S.; Dr.

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

0

Issued Date

2019

Resource Type

Article

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application/pdf

ISSN

21949379

DOI

10.1055/a-0968-1150

Other identifier(s)

2-s2.0-85075814506

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Scopus

Bibliographic Citation

Drug Research. Vol 69, No.12 (2019), p.671-682

Suggested Citation

Makarasen A., Kuno M., Patnin S., Reukngam N., Khlaychan P., Deeyohe S., Intachote P., Saimanee B., Sengsai S., Boonsri P., Chaivisuthangkura A., Sirithana W., Techasakul S., Dr. Molecular Docking Studies and Synthesis of Amino-oxy-diarylquinoline Derivatives as Potent Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors. Drug Research. Vol 69, No.12 (2019), p.671-682. doi:10.1055/a-0968-1150 Retrieved from: https://hdl.handle.net/20.500.14740/5695

Title

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

Author(s)

Makarasen A.
Kuno M.
Patnin S.
Reukngam N.
Khlaychan P.
Deeyohe S.
Intachote P.
Saimanee B.
Sengsai S.
Boonsri P.
Chaivisuthangkura A.
Sirithana W.
Techasakul S.
Dr.

Abstract

In 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 π-π 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 μM concentration. Interestingly, 8a was highly cytotoxicity against MOLT-3 (acute lymphoblastic leukemia), with an IC 50 of 4.63±0.62 μg/mL, which was similar with that in EFV and TMC278 (IC 50 7.76±0.37 and 1.57±0.20 μg/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.

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https://hdl.handle.net/20.500.14740/5695

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Scopus: Year 1983-2021

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

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