Fullerene derivatives as dual inhibitors of HIV-1 reverse transcriptase and protease.

Authors :: Yasuno T
Ohe T
Kataoka H
Hashimoto K
Ishikawa Y
Furukawa K
Tateishi Y
Kobayashi T
Takahashi K
Nakamura S
Mashino T
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2021 Jan 01; Vol. 31, pp. 127675. Date of Electronic Publication: 2020 Nov 05.
Publication Year :: 2021
Abstract: In the present study, we newly synthesized three types of novel fullerene derivatives: pyridinium-type derivatives trans-3a and 4a-5b, piperidinium-type derivative 9, and proline-type derivatives 10a-12. Among the assessed compounds, 5a, 10e, 10f, 10i, 11a-d, and 12 were found to inhibit both HIV reverse transcriptase and HIV protease (HIV-PR), with IC <subscript>50</subscript> values in the low micromolar range being observed. Regarding HIV-PR inhibition activity, proline-type derivatives 11a-11d and 12, bearing an alkyl chain between the hydroxylmethylcarbonyl (HMC) moiety and pyrrolidine ring, were more potent than other derivatives. This result might indicate that connecting HMC moieties with proline-type fullerene derivatives through properly sized alkyl chain leads to improved HIV-PR inhibitory activity.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Subjects :: Dose-Response Relationship, Drug
Fullerenes chemistry
HIV Protease Inhibitors chemical synthesis
HIV Protease Inhibitors chemistry
HIV Reverse Transcriptase metabolism
Molecular Structure
Pyridinium Compounds chemistry
Reverse Transcriptase Inhibitors chemical synthesis
Reverse Transcriptase Inhibitors chemistry
Structure-Activity Relationship
Fullerenes pharmacology
HIV Protease metabolism
HIV Protease Inhibitors pharmacology
HIV Reverse Transcriptase antagonists & inhibitors
Pyridinium Compounds pharmacology
Reverse Transcriptase Inhibitors pharmacology

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