TY - JOUR
T1 - Fullerene derivatives as dual inhibitors of HIV-1 reverse transcriptase and protease
AU - Yasuno, Takumi
AU - Ohe, Tomoyuki
AU - Kataoka, Hiroki
AU - Hashimoto, Kosho
AU - Ishikawa, Yumiko
AU - Furukawa, Keigo
AU - Tateishi, Yasuhiro
AU - Kobayashi, Toi
AU - Takahashi, Kyoko
AU - Nakamura, Shigeo
AU - Mashino, Tadahiko
N1 - Funding Information:
This research was supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research) from AMED under Grant Number JP20am0101089 .
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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 IC50 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.
AB - 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 IC50 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.
KW - Fullerene
KW - HIV protease
KW - HIV reverse transcriptase
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U2 - 10.1016/j.bmcl.2020.127675
DO - 10.1016/j.bmcl.2020.127675
M3 - Article
C2 - 33161121
AN - SCOPUS:85096168979
SN - 0960-894X
VL - 31
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
M1 - 127675
ER -
