Mechanism of interaction of novel indolylarylsulfone derivatives with K103N and Y181I mutant HIV-1 reverse transcriptase in complex with its substrates

Antiviral Chemistry and Chemotherapy

Volumn 22, Issue 3, 2012, Pages 107-118

  Samuele, Alberta ^a   Bisi, Sara ^a   Kataropoulou, Alexandra ^a   La Regina, Giuseppe ^b   Piscitelli, Francesco ^b   Gatti, Valerio ^b   Silvestri, Romano ^b   Maga, Giovanni ^a  

^a CNR   (Italy)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; RS 1762; RS 1765; RS 2862; RS 2911; RS 3084; UNCLASSIFIED DRUG; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; REVERSE TRANSCRIPTASE, HUMAN IMMUNODEFICIENCY VIRUS 1; SULFONE;

ARTICLE; DRUG ANALYSIS; ENZYME INHIBITOR INTERACTION; ENZYME SUBSTRATE COMPLEX; GENE MUTATION; HUMAN; HUMAN CELL; PRIORITY JOURNAL; STEADY STATE; WILD TYPE; ANTIVIRAL RESISTANCE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; ENZYME SPECIFICITY; ENZYMOLOGY; GENETICS; HUMAN IMMUNODEFICIENCY VIRUS 1; METABOLISM; MUTATION; STRUCTURE ACTIVITY RELATION;

ANTI-HIV AGENTS; DRUG RESISTANCE, VIRAL; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; MODELS, MOLECULAR; MUTATION; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; SULFONES;

EID: 84861534913     PISSN: 09563202     EISSN: None     Source Type: Journal    
DOI: 10.3851/IMP1855     Document Type: Article

References (21)

1. Siliciano RF. What do we need to do to cure HIV infection. Top HIV Med 2010; 18:104-108.
2. Este JA, Cihlar T. Current status and challenges of antiretroviral research and therapy. Antiviral Res 2010; 85:25-33.
3. Arnold E, Das K, Ding J, et al. Targeting HIV reverse transcriptase for anti-AIDS drug design: structural and biological considerations for chemotherapeutic strategies. Drug Des Discov 1996; 13:29-47.
4. Erickson J W, Burt SK. Structural mechanisms of HIV drug resistance. Annu Rev Pharmacol Toxicol 1996; 36:545-571.
5. Sluis-Cremer N, Arion D, Parniak MA. Molecular mechanisms of HIV-1 resistance to nucleoside reverse transcriptase inhibitors (NRTIs). Cell Mol Life Sci 2000; 57:1408-1422.
6. Sarafanos SG, Marchand B, Das K, et al. Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition. J Mol Biol 2009; 385:693-713.
7. Ren J, Stammers DK. Structural basis for drug resistance mechanisms for non-nucleoside inhibitors of HIV reverse transcriptase. Virus Res 2008; 134:157-170.
8. Maga G, Ramunno A, Nacci V, et al. The stereoselective targeting of a specifc enzyme-substrate complex is the molecular mechanism for the synergic inhibition of HIV-1 reverse transcriptase by (R)-(-)-PPO464: a novel generation of nonnucleoside inhibitors. J Biol Chem 2001; 276:44653-44662.
9. Baldanti F, Paolucci S, Maga G, et al. Nevirapine-selected mutations Y181I/C of HIV-1 reverse transcriptase confer cross-resistance to stavudine. AIDS 2003; 17:1568-1570.
10. Paolucci S, Baldanti F, Campanini G, et al. NNRTI-selected mutations at codon 190 of human immunodeficiency virus type 1 reverse transcriptase decrease susceptibility to stavudine and zidovudine. Antiviral Res 2007; 76:99-103.
11. Fattorusso C, Gemma S, Butini S, et al. Specific targeting highly conserved residues in the HIV-1 reverse transcriptase primer grip region. Design, synthesis, and biological evaluation of novel, potent, and broad spectrum NNRTIs with antiviral activity. J Med Chem 2005; 48:7153-7165.
12. Samuele A, Kataropoulou A, Viola M, et al. Non-nucleoside HIV-1 reverse transcriptase inhibitors di-halo-indolyl aryl sulfones achieve tight binding to drug-resistant mutants by targeting the enzyme-substrate complex. Antiviral Res 2009; 81:47-55.
13. Silvestri R, De Martino G, La Regina G, et al. Novel indolyl aryl sulfones active against HIV-1 carrying NNRTI resistance mutations: synthesis and SAR studies. J Med Chem 2003; 46:2482-2493.
14. Cancio R, Silvestri R, Ragno R, et al. High potency of indolyl aryl sulfone nonnucleoside inhibitors towards drug-resistant human immunodeficiency virus type 1 reverse transcriptase mutants is due to selective targeting of different mechanistic forms of the enzyme. Antimicrob Agents Chemother 2005; 49:4546-4554.
15. De Martino G, La Regina G, Ragno R, et al. Indolyl aryl sulphones as HIV-1 non-nucleoside reverse transcriptase inhibitors: synthesis, biological evaluation and binding mode studies of new derivatives at indole-2-carboxamide. Antivir Chem Chemother 2006; 17:59-77.
16. Piscitelli F, Coluccia A, Brancale A, et al. Indolylarylsulfones bearing natural and unnatural amino acids. Discovery of potent inhibitors of HIV-1 non-nucleoside wild type and resistant mutant strains reverse transcriptase and coxsackie B4 virus. J Med Chem 2009; 52:1922-1934.
17. Vingerhoets J, Tambuyzer L, Azijn H, et al. Resistance profle of etravirine: combined analysis of baseline genotypic and phenotypic data from the randomized, controlled Phase III clinical studies. AIDS 2010; 24:503-514.
18. Di Vincenzo P, Rusconi S, Adorni F, et al. Prevalence of mutations and determinants of genotypic resistance to etravirine (TMC125) in a large Italian resistance database (ARCA). HIV Med 2010; 11:530-534.
19. La Regina G, Coluccia A, Brancale A, et al. Indolylarylsulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: new cyclic substituents at indole-2-carboxamide. J Med Chem 2011; 54:1587-1598.
20. Maga G, Ubiali D, Salvetti R, Pregnolato M, Spadari S. Selective interaction of the human immunodefciency virus type 1 reverse transcriptase nonnucleoside inhibitor efavirenz and its thio-substituted analog with different enzyme-substrate complexes. Antimicrob Agents Chemother 2000; 44:1186-1194.
21. Das K, Lewi PJ, Huges SH, Arnold S. Crystallography and the design of anti-AIDS drugs: conformational fexibility and positional adaptability are important in the design of non-nucleoside HIV-1 reverse transcriptase inhibitors. Prog Biophys Mol Biol 2005; 88:209-231.