Synthesis and anti-hiv-1 activity of a novel series of aminoimidazole analogs

Swastika Ganguly; Sankaran Murugesan; Naru Prasanthi; Onur Alptürk; Brian Herman; Nicolas Sluis-Cremer

doi:10.2174/157018010791163424

Synthesis and anti-hiv-1 activity of a novel series of aminoimidazole analogs

Swastika Ganguly^*
, Sankaran Murugesan
, Naru Prasanthi
, Onur Alptürk
, Brian Herman
, Nicolas Sluis-Cremer

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

There is still an urgent need to develop nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) with a high-genetic barrier to resistance that facilitate patient adherence and allow durable suppression of HIV-1 replication. In this study, we describe the synthesis of a novel series of N-aminoimidazole (NAIM) analogs. Each of the NAIM analogs display potent activity against wild-type recombinant purified HIV-1 RT as well as RTs containing the K103N or Y181C resistance mutations. The analogs, however, do not exhibit significant antiviral activity in cell culture and were, in general, cytotoxic. Nevertheless, these data suggest that the NAIM backbone may provide a suitable scaffold from which inhibitors active against NNRTI-resistant HIV-1 could be developed.

Original language	English
Pages (from-to)	318-323
Number of pages	6
Journal	Letters in Drug Design and Discovery
Volume	7
Issue number	5
DOIs	https://doi.org/10.2174/157018010791163424
Publication status	Published - 2010
Externally published	Yes

Keywords

HIV
Molecular modeling
N-aminoimidazole
NNRTI
Reverse transcriptase
Synthesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2174/157018010791163424

Cite this

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abstract = "There is still an urgent need to develop nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) with a high-genetic barrier to resistance that facilitate patient adherence and allow durable suppression of HIV-1 replication. In this study, we describe the synthesis of a novel series of N-aminoimidazole (NAIM) analogs. Each of the NAIM analogs display potent activity against wild-type recombinant purified HIV-1 RT as well as RTs containing the K103N or Y181C resistance mutations. The analogs, however, do not exhibit significant antiviral activity in cell culture and were, in general, cytotoxic. Nevertheless, these data suggest that the NAIM backbone may provide a suitable scaffold from which inhibitors active against NNRTI-resistant HIV-1 could be developed.",

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T1 - Synthesis and anti-hiv-1 activity of a novel series of aminoimidazole analogs

AU - Ganguly, Swastika

AU - Murugesan, Sankaran

AU - Prasanthi, Naru

AU - Alptürk, Onur

AU - Herman, Brian

AU - Sluis-Cremer, Nicolas

PY - 2010

Y1 - 2010

N2 - There is still an urgent need to develop nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) with a high-genetic barrier to resistance that facilitate patient adherence and allow durable suppression of HIV-1 replication. In this study, we describe the synthesis of a novel series of N-aminoimidazole (NAIM) analogs. Each of the NAIM analogs display potent activity against wild-type recombinant purified HIV-1 RT as well as RTs containing the K103N or Y181C resistance mutations. The analogs, however, do not exhibit significant antiviral activity in cell culture and were, in general, cytotoxic. Nevertheless, these data suggest that the NAIM backbone may provide a suitable scaffold from which inhibitors active against NNRTI-resistant HIV-1 could be developed.

AB - There is still an urgent need to develop nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) with a high-genetic barrier to resistance that facilitate patient adherence and allow durable suppression of HIV-1 replication. In this study, we describe the synthesis of a novel series of N-aminoimidazole (NAIM) analogs. Each of the NAIM analogs display potent activity against wild-type recombinant purified HIV-1 RT as well as RTs containing the K103N or Y181C resistance mutations. The analogs, however, do not exhibit significant antiviral activity in cell culture and were, in general, cytotoxic. Nevertheless, these data suggest that the NAIM backbone may provide a suitable scaffold from which inhibitors active against NNRTI-resistant HIV-1 could be developed.

KW - HIV

KW - Molecular modeling

KW - N-aminoimidazole

KW - NNRTI

KW - Reverse transcriptase

KW - Synthesis

UR - https://www.scopus.com/pages/publications/77953694593

U2 - 10.2174/157018010791163424

DO - 10.2174/157018010791163424

M3 - Article

AN - SCOPUS:77953694593

SN - 1570-1808

VL - 7

SP - 318

EP - 323

JO - Letters in Drug Design and Discovery

JF - Letters in Drug Design and Discovery

IS - 5

ER -

Synthesis and anti-hiv-1 activity of a novel series of aminoimidazole analogs

Abstract

Keywords

UN SDGs

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