Tigeciklin

Tigeciklin
(IUPAC) ime
	N-[(5aR,6aS,7S,9Z,10aS)-9-[amino(hidroksi)metiliden]-4,7-bis(dimetilamino)-1,10a,12-trihidroksi-8,10,11-triokso-5,5a,6,6a,7,8,9,10,10a,11-dekahidrotetracen-2-il]-2-(tert-butilamino)acetamid
Klinički podaci
Robne marke	Tigacil
AHFS/Drugs.com	Monografija
Identifikatori
CAS broj	220620-09-7
ATC kod	J01AA12
PubChem	5282044
DrugBank	DB00560
ChemSpider	10482314
UNII	70JE2N95KR
KEGG	D01079
ChEBI	CHEBI:149836
ChEMBL	CHEMBL376140
Hemijski podaci
Formula	C29H39N5O8
Mol. masa	585,65 g/mol
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C29H39N5O8/c1-28(2,3)31-11-17(35)32-15-10-16(33(4)5)13-8-12-9-14-21(34(6)7)24(38)20(27(30)41)26(40)29(14,42)25(39)18(12)23(37)19(13)22(15)36/h10,12,14,21,31,36,38-39,42H,8-9,11H2,1-7H3,(H2,30,41)(H,32,35)/t12-,14-,21-,29-/m0/s1 ; Key: FPZLLRFZJZRHSY-HJYUBDRYSA-N
Sinonimi	N-[(5aR,6aS,7S,9Z,10aS)-9-(amino-hydroxy-methylidene)-4,7-bis(dimethylamino)-1,10a,12-trihydroxy-8,10,11-trioxo-5a,6,6a,7-tetrahydro-5H-tetracen-2-yl]-2-(tert-butylamino)acetamide
Farmakokinetički podaci
Bioraspoloživost	NA
Vezivanje za proteine plazme	71-89%
Metabolizam	ne metabolizuje se
Poluvreme eliminacije	42,4 sata
Izlučivanje	59% bilijarno, 33% renalno
Farmakoinformacioni podaci
Trudnoća	D(AU) D(US)
Pravni status	Samo na recept (S4) (AU) ℞-only (SAD)
Način primene	IV only

Tigeciklin je glicilciklinski antibiotik^[6]^[7] koji je razvila kompanija Francis Tali^[8] i koji proizvodi i prodaje Wyeth pod iemnom Tigacil. Ovaj lek je FDA odobrila 2005. On je razvijen u responsu na rastuću prevalenciju otpornosti na antibiotike kod bakterija poput Staphylococcus aureus i Acinetobacter baumannii. Enterobacteriaceae otporne na višestruke lekove usled dejstva enzima Nju Delhi metalo-beta-laktamaza su isto tako podložen tigeciklinu.^[9]

Struktura

Ovaj antibiotik je prvi klinički dostupan lek u novoj klasi antibiotika zavanih glicilciklini. On je strukturno sličan sa tetraciklinima po tome što sadrži centralni skeleton sa četiri prstena. On je derivat minociklina. Tigeciklin je supstitutuisan na D-9 poziciji za šta se smatra da uzrokuje širok spektar aktivnosti.

Mehanizam dejstva

Tigeciklin je bakteriostatik i inhibitor proteinske sinteze putem vezivanja za 30S ribozomalnu podjedinicu bakterija čime blokira pristup Aminoacil-tRNK u A mesto ribozoma tokom prokariotske translacije.^[10]

Sinonimi

GAR-936^[11]
Tigacil

Reference

↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit
↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit
↑ Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.
↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit
↑ Rose W, Rybak M (2006). „Tigecycline: first of a new class of antimicrobial agents.”. Pharmacotherapy 26 (8): 1099–110. DOI:10.1592/phco.26.8.1099. PMID 16863487.
↑ Kasbekar N (2006). „Tigecycline: a new glycylcycline antimicrobial agent.”. Am J Health Syst Pharm 63 (13): 1235–43. DOI:10.2146/ajhp050487. PMID 16790575.
↑ Projan, Steven J (January 2010). „Francis Tally and the discovery and development of tigecycline: a personal reminiscence”. Clin. Infect. Dis. (United States) 50 Suppl 1: S24–5. DOI:10.1086/647941. PMID 20067389.
↑ Kumarasamy et. al.; Toleman, Mark A; Walsh, Timothy R; Bagaria, Jay; Butt, Fafhana; Balakrishnan, Ravikumar; Chaudhary, Uma; Doumith, Michel i dr.. (2010). „Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study”. The Lancet Infectious Diseases 10 (9): 597–602. DOI:10.1016/S1473-3099(10)70143-2. PMC 2933358. PMID 20705517.
↑ Tigecycline: A Novel Broad-Spectrum Antimicrobial: Pharmacology and Mechanism of Action Christine M. Slover, PharmD, Infectious Diseases Fellow, Keith A. Rodvold, PharmD and Larry H. Danziger, PharmD, Professor, Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL
↑ Betriu C, Rodríguez-Avial I, Sánchez BA, Gómez M, Picazo JJ (2002). „Comparative in vitro activities of tigecycline (GAR-936) and other antimicrobial agents against Stenotrophomonas maltophilia”. J Antimicrob Chemother 50 (5): 758–59. DOI:10.1093/jac/dkf196. PMID 12407139.

Vanjske veze

	Portal Medicina
	Portal Hemija

Tygacil ( tigecycline iv ): Antibiotic for Skin Infections Arhivirano 2008-07-06 na Wayback Machine-u

[1] Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit

[2] Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.

[3] Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit

[4] Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.

[5] Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit

[6] Rose W, Rybak M (2006). „Tigecycline: first of a new class of antimicrobial agents.”. Pharmacotherapy 26 (8): 1099–110. DOI:10.1592/phco.26.8.1099. PMID 16863487.

[7] Kasbekar N (2006). „Tigecycline: a new glycylcycline antimicrobial agent.”. Am J Health Syst Pharm 63 (13): 1235–43. DOI:10.2146/ajhp050487. PMID 16790575.

[8] Projan, Steven J (January 2010). „Francis Tally and the discovery and development of tigecycline: a personal reminiscence”. Clin. Infect. Dis. (United States) 50 Suppl 1: S24–5. DOI:10.1086/647941. PMID 20067389.

[Kumarasamy-9] Kumarasamy et. al.; Toleman, Mark A; Walsh, Timothy R; Bagaria, Jay; Butt, Fafhana; Balakrishnan, Ravikumar; Chaudhary, Uma; Doumith, Michel i dr.. (2010). „Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study”. The Lancet Infectious Diseases 10 (9): 597–602. DOI:10.1016/S1473-3099(10)70143-2. PMC 2933358. PMID 20705517.

[10] Tigecycline: A Novel Broad-Spectrum Antimicrobial: Pharmacology and Mechanism of Action Christine M. Slover, PharmD, Infectious Diseases Fellow, Keith A. Rodvold, PharmD and Larry H. Danziger, PharmD, Professor, Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL

[11] Betriu C, Rodríguez-Avial I, Sánchez BA, Gómez M, Picazo JJ (2002). „Comparative in vitro activities of tigecycline (GAR-936) and other antimicrobial agents against Stenotrophomonas maltophilia”. J Antimicrob Chemother 50 (5): 758–59. DOI:10.1093/jac/dkf196. PMID 12407139.

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