Structure-Activity Relationship of Pyrrolyl Diketo Acid Derivatives as Dual Inhibitors of HIV-1 Integrase and Reverse Transcriptase Ribonuclease H Domain

被引：77

作者：

Crucitti, Giuliana Cuzzucoli ^{[1
]}

Metifiot, Mathieu

Pescatori, Luca ^{[1
]}

Messore, Antonella ^{[1
]}

Madia, Valentina Noemi ^{[1
]}

Pupo, Giovanni ^{[1
]}

Saccoliti, Francesco ^{[1
]}

Scipione, Luigi ^{[1
]}

Tortorella, Silvano ^{[1
]}

Esposito, Francesca ^{[4
]}

Corona, Angela ^{[4
]}

Cadeddu, Marta ^{[4
]}

Marchand, Christophe ^{[2
,3
]}

Pommier, Yves ^{[2
,3
]}

Tramontano, Enzo ^{[4
]}

Costi, Roberta ^{[1
]}

Di Santo, Roberto ^{[1
]}

机构：

[1] Sapienza Univ Roma, Dipartimento Chim & Tecnol Farmaco, Ist Pasteur, Fdn Cenci Bolognetti, I-00185 Rome, Italy

[2] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA

[3] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[4] Univ Cagliari, Dept Life & Environm Sci, I-09124 Cagliari, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 58卷 / 04期

关键词：

VIRUS TYPE-1 INTEGRASE; RNASE-H; MONOAMINE-OXIDASE; STRAND TRANSFER; HYDROXYTROPOLONES; REPLICATION; RALTEGRAVIR; POLYMERASE; RESISTANT; 3-KINASE;

D O I：

10.1021/jm501799k

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The development of HIV-1 dual inhibitors is a highly innovative approach aimed at reducing drug toxic side effects as well as therapeutic costs. HIV-1 integrase (IN) and reverse transcriptase-associated ribonuclease H (RNase H) are both selective targets for HIV-1 chemotherapy, and the identification of dual IN/RNase H inhibitors is an attractive strategy for new drug development. We newly synthesized pyrrolyl derivatives that exhibited good potency against IN and a moderate inhibition of the RNase H function of RT, confirming the possibility of developing dual HIV-1 IN/RNase H inhibitors and obtaining new information for the further development of more effective dual HIV-1 inhibitors.

引用

页码：1915 / 1928

页数：14

共 48 条

[1]

Alberola A., 1990, J CHEM SOC P1, V10, P2681

[2] Flavocoxid, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, blunts pro-inflammatory phenotype activation in endotoxin-stimulated macrophages [J].

Altavilla, D. ;

Squadrito, F. ;

Bitto, A. ;

Polito, F. ;

Burnett, B. P. ;

Di Stefano, V. ;

Minutoli, L. .

BRITISH JOURNAL OF PHARMACOLOGY, 2009, 157 (08) :1410-1418

[3]

Anguillera A., 1987, CAN J CHEM, V65, P1165

[4]

Beare KD, 2012, CURR MED CHEM, V19, P1177

[5] 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as inhibitors of HIV-1 integrase and reverse transcriptase RNase H domain: Influence of the alkylation of position 4 [J].

Billamboz, Muriel ;

Bailly, Fabrice ;

Lion, Cedric ;

Calmels, Christina ;

Andreola, Marie-Line ;

Witvrouw, Myriam ;

Christ, Frauke ;

Debyser, Zeger ;

De Luca, Laura ;

Chimirri, Alba ;

Cotelle, Philippe .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (02) :535-546

[6] Design, Synthesis, and Biological Evaluation of a Series of 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as Dual Inhibitors of Human Immunodeficiency Virus Type 1 Integrase and the Reverse Transcriptase RNase H Domain [J].

Billamboz, Muriel ;

Bailly, Fabrice ;

Barreca, Maria Letizia ;

De Luca, Laura ;

Mouscadet, Jean-Francois ;

Calmels, Christina ;

Andreola, Marie-Line ;

Witvrouw, Myriam ;

Christ, Frauke ;

Debyser, Zeger ;

Cotelle, Philippe .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (24) :7717-7730

[7] Coumarins derivatives as dual inhibitors of acetylcholinesterase and monoamine oxidase [J].

Brühlmann, C ;

Ooms, F ;

Carrupt, PA ;

Testa, B ;

Catto, M ;

Leonetti, F ;

Altomare, C ;

Carotti, A .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (19) :3195-3198

[8] Selective inhibition of HIV-1 reverse transcriptase-associated ribonuclease H activity by hydroxylated tropolones [J].

Budihas, SR ;

Gorshkova, I ;

Gaidamakov, S ;

Wamiru, A ;

Bona, MK ;

Parniak, MA ;

Crouch, RJ ;

McMahon, JB ;

Beutler, JA ;

Le Grice, SFJ .

NUCLEIC ACIDS RESEARCH, 2005, 33 (04) :1249-1256

[9] Structural insights into the retroviral DNA integration apparatus [J].

Cherepanov, Peter ;

Maertens, Goedele N. ;

Hare, Stephen .

CURRENT OPINION IN STRUCTURAL BIOLOGY, 2011, 21 (02) :249-256

[10] Structure-Activity Analysis of Vinylogous Urea Inhibitors of Human Immunodeficiency Virus-Encoded Ribonuclease H [J].

Chung, Suhman ;

Wendeler, Michaela ;

Rausch, Jason W. ;

Beilhartz, Greg ;

Gotte, Matthias ;

O'Keefe, Barry R. ;

Bermingham, Alun ;

Beutler, John A. ;

Liu, Shixin ;

Zhuang, Xiaowei ;

Le Grice, Stuart F. J. .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2010, 54 (09) :3913-3921

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